atypical parathyroid adenoma complicated with protracted hungry

Case ReportAtypical Parathyroid Adenoma Complicated withProtracted Hungry Bone Syndrome after SurgeryA Case Report and Literature Review

Oacutescar Alfredo Juaacuterez-Leoacuten1 Miguel Aacutengel Goacutemez-Saacutemano1 Daniel Cuevas-Ramos1

Paloma Almeda-Valdeacutes1 Manuel Alejandro Loacutepez-Flores A La Torre2

Alfredo Adolfo Reza-Albarraacuten1 and Francisco Javier Goacutemez-Peacuterez1

1Endocrinology and Metabolism Department Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran14080 Mexico City Mexico2School of Medicine Universidad Panamericana 03920 Mexico City Mexico

Correspondence should be addressed to Francisco Javier Gomez-Perez gomezperezfcogmailcom

Received 10 August 2015 Accepted 26 October 2015

Academic Editor Hidetoshi Ikeda

Copyright copy 2015 Oscar Alfredo Juarez-Leon et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Hungry Bone Syndrome refers to the severe and prolonged hypocalcemia and hypophosphatemia following parathyroidectomy inpatients with hyperparathyroidism We present the case of an eighteen-year-old woman with a four-year history of hyporexiapolydipsia weight loss growth retardation and poor academic performance The diagnostic work-up demonstrated primaryhyperparathyroidism with hypercalcemia of 1336mgdL a PTH level of 2551 pgmL bone brown tumors and microcalcificationswithin pancreas and kidneys Neck ultrasonography revealed a parathyroid adenoma of 33 times 14 times 14mm also identified on 99Tc-sestamibi scan Bone densitometry showed decreased 119885-Score values (total lumbar 119885-Score of minus42) A right hemithyroidectomyand right lower parathyroidectomy were performed Pathological examination showed an atypical parathyroid adenoma of 38 g ofweight and 28 cm in diameter After surgery she developed hypocalcemia with tetany and QTc interval prolongation The patientrequired 3 months of oral and intravenous calcium supplementation due to Hungry Bone Syndrome (HBS) After 42 months sheis still under oral calcium Usually HBS lasts less than 12 monthsTherefore we propose the term ldquoProtracted HBSrdquo in patients withparticularly long recovery of 1 year We present a literature review of the diagnosis pathophysiology and treatment of HBS

1 Introduction

The Hungry Bone Syndrome (HBS) was first described byAlbright and Reifenstein in 1950 in patients with hyper-parathyroidism with a severe and prolonged hypocalcemiaafter parathyroidectomy [1]

Most HBS definitions consider clinical manifestations ofhypocalcemia and biochemical variables including hyper-parathyroidism requiring surgery hypophosphatemia andhypomagnesemia Some authors denote HBS when patientsdevelop postoperative hypocalcemia (lt85mgdL) a simul-taneous inorganic phosphate value of lt30mgdL [2]and hypocalcemia longer than 4 days requiring calcium

supplementation despite optimization of supportive therapywith normal vitamin D levels [3 4]

Parathyroid hormone (PTH) and calcitriol(112057225[OH]

2D3) regulate calcium and phosphate homeosta-

sis PTH is secreted in response to hypocalcemia after beingsensed by the parathyroid calcium-sensing receptor (CaSR)[5] PTH receptors are mainly present in kidney and bonetissue [6] and when activated they increase bone calciumefflux and decrease renal excretion to maintain normalserum calcium concentrations The HBS pathophysiologybegins with elevated PTH production (primary secondaryor tertiary hyperparathyroidism) which augments bonemetabolism and calcium turnover leading to increased

Hindawi Publishing CorporationCase Reports in EndocrinologyVolume 2015 Article ID 757951 8 pageshttpdxdoiorg1011552015757951

2 Case Reports in Endocrinology

Table 1 Laboratory findings at hospital admission and at last outpatient follow-up visit

Hospitalization[February 2010]

Follow-up[November 2013] Reference values

Serum calcium [mgdL] 121 89 86ndash99Corrected serum calcium [mgdL]lowast 126 79Serum phosphate [mgdL] 27 3 27ndash45Serum magnesium [mgdL] 13 2 19ndash27Serum albumin [gdL] 34 52 35ndash57Serum creatinine [mgdL] 483 105 042ndash109Creatinine clearance [mlmin173m2] 12 76 ge90PTH [pgmL] 2551 917 12ndash8825-OH vitamin D [ngmL] 13 259 30ndash100Alkaline phosphatase [IUL] 4410 126 34ndash104Urinary calcium [mgday] 213 22 100ndash300Urinary phosphorus [mgday] 413 524 lt1000Prolactin [ngmL] 126 mdash 264ndash1313FSH [mIUmL] 44 mdash 385ndash878(follicular phase)

LH [mIUmL] 17 mdash 212ndash1089(follicular phase)

Estradiol [pgmL] 3613 mdash 12ndash40(follicular phase)

T3 [nmolL] 178 mdash 064ndash181T4 [nmolL] 6933 mdash 66ndash181TSH [120583UImL] 185 mdash 03ndash5Thyroglobulin [ngmL] 57 mdash 0ndash368ACTH [pgmL] 19 mdash 10ndash100Morning cortisol [120583gdL] 1576 67ndash226PTH parathyroid hormonelowastCorrected calcium with albumin using the following formula Ca2+corrected = Ca2+measured + 08 times [4 minus albuminmeasured]

serum calcium levels Treatment of primary hyperparathy-roidism often requires surgical resection of an adenomacausing a sudden halt in bone turnover Consequently amarked depletion of serum circulating calcium phosphateand magnesium is seen due to bone remineralization [2]

The most common etiologies associated with HBS aresecondary and primary hyperparathyroidism [3 7 8] Otherless frequent causes are parathyroid carcinoma drugs mul-tiple endocrine neoplasia and metastatic prostate cancer [9ndash14]

Here we present a clinical case of an unusual long-lasting HBS developed in a female patient with primaryhyperparathyroidism after surgical treatment of an atypicaladenoma

2 Case Presentation

An 18-year-old previously healthy woman presented at ourinstitution after a four-year history of hyporexia polydip-sia weight loss growth retardation and poor academicperformance One month prior to presentation outpatientlaboratory analysis revealed increased serum calcium andparathyroid hormone (PTH) She did not have any othersignificant personal or family history

She was admitted to our hospital in February 2010 Onphysical examination her height was 140m and weight was

30 kg Her vital signs were within normal limits She pre-sented with a marked cervical kyphosis

Relevant laboratory results showed hypercalcemia(1336mgdL normal 86ndash99mgdL) elevated PTH (2551 pgmL normal 12ndash88 pgmL) elevated alkaline phosphataselevel (4410 IUL normal 34ndash104 IUL) hypercalciuria (uri-nary calcium of 213mg24H normal 100ndash250mg24H) lowcreatinine clearance (2584mLmin173m2 normalge90mLmin173m2) and low 25[OH]D

3circulating level (13 ngmL

normal 30ndash100 ngmL) The laboratory findings at hospitaladmission and last follow-up visit are summarized in Table 1Biochemical approach was further completed with prolactin126 ngmL FSH 44mIUmL LH 17mIUmL estradiol3613 pgmL T3 178 nmolL T4 6933 nmolL TSH 185 120583UImL thyroglobulin 57 ngmL ACTH 19 pgmL andmorningcortisol 1576 120583gdL all within normal limits

Skeletal X-rays showed skull with ldquosalt and pepperrdquolesions vertebral compression fractures brown tumorswithin the left humerus and profuse calcifications within thepancreas and kidneys (Figure 1) The patient did not referto abdominal pain nor any symptomatology related toendocrine and exocrine pancreatic insufficiency The elec-trocardiogram was unremarkable Abdominal ultrasoundrevealed kidney stones causing bilateral dilation of the renalpelvis Neck ultrasonography showed microcalcificationswithin a large echogenic mass posterior to the right lobe of

Case Reports in Endocrinology 3

(a) (b)

Figure 1 Abdominal computed tomography (CT) on admission (a) Diffuse pancreatic calcifications (b) bilateral kidney calcifications onaxial computed tomography Findings are marked with white arrow heads

(a) (b)

Figure 2 Neck ultrasonography on admission (a) Large echogenic mass dorsal to the right lobe of the thyroid gland (b) Doppler effectshowing polar vessel finding present in most adenomas Findings are marked with white arrow heads

the thyroid gland of 33times 14times 14mm Figure 2 A 25mCi 99Tc-sestamibi scintigraphy reported persistence of the radionu-clide material at 120 minutes in the right inferior parathyroidgland at the same location of the mass shown in the USFigure 3 Bone densitometry showed decreased 119885-Score val-ues (total lumbar 119885-Score of minus42) Table 2 Primary hyper-parathyroidism secondary to a large parathyroid tumor wasdiagnosed

For HBS prophylaxis before surgery she received a400000 IU of vitamin D2 (Drisdol) (ergocalciferol) and1mg of calcitriol Right hemithyroidectomy with right lowerparathyroidectomy was performed A tumor of 28 cm with38 g of weight was resected Pathological revision reporteda focal lesion containing parathyroid tissue it infiltrated thenodule capsule without trespassing it and the diagnosiswas consistent with an atypical parathyroid adenoma Twolymphnodes demonstrated follicular hyperplasiaDespite theadministration of vitamin D (50000 per week) and calcitriol075mg per day after surgery the 25-hydroxyvitaminD levelsnever reached a value above 30 125-dihydroxy vitaminDwasnot measured

Postsurgical laboratory analysis showed PTH values of313 pgmL serum calciumof 85mgdL phosphate of 19mgdL and magnesium of 18mgdL on physical examination

Table 2 Densitometry values on admission and at the last follow-upvisit as an outpatient The most affected segment is presentedlowast

Hospitalization Follow-up[February 2010] [November 2013]

Lumbar BMD L1 Total L1 Total[gcm2] 053 0551 1061 107119885-Score mdash minus42 14 04119879 score minus36 minus45 12 02Hip BMD Neck Total Neck Total[gcm2] 041 0481 0939 0998119885-Scorelowast mdash mdash 06 04119879 score minus39 minus36 05 03Osteoporosis is diagnosed in young adults when both 119885-score ltminus20 andfractures are presentlowastDue to the age of presentation baseline119885-scores could not be obtainedwiththe equipment used in our patient

she presented upper extremity distal contractures oro-mandibular dystonia Chvostek andTrousseau signs andQTcinterval prolongation PTH levels reached up to 486 pgmLafter 1 month coexisting with hypophosphatemia of 27mgdL At last follow-up PTH serum levels were between 80


20min 120min

(a)

20min 120min

(b)

Figure 3 Neck scintigraphies with 25 mCi of 99Tc-sestamibi with 01015840 and 1201015840 wash-out sequences (a) 2010 Admission Scintigraphy 1201015840washout sequence shows residual capitation from right lower thyroid lobe suggesting a parathyroid adenoma (b) 2013 postparathyroidectomycontrol scintigraphy 1201015840 wash-out sequence shows no apparent residual captation Findings are marked with white arrow heads

and 90 pgmL Table 2 She developed a prolonged and severeHBS that required 3 months with oral and intravenous cal-cium supplementationThe calcium IV infusion was stoppedthree months later High PTH levels with hypocalcemiabut also hypophosphatemia ruled out hypoparathyroidismldquoProtractedrdquoHBSwas therefore diagnosedDuring her hospi-talization she underwent two episodes of lithotripsy as treat-ment for the kidney stones Serum calcium phosphate andmagnesium levels during hospitalization and follow-up areshown in Figure 4

After 42 months of treatment bone densitometry scoresimproved within normal limits Table 2 As an outpatientsince 2010 she has been receiving an average of 1197mg of oralelemental calcium 1600 units of vitamin D and 3 grams ofmagnesium sulfate per day She was kept under close medicalevaluation as an outpatient Unfortunately in November 2013the patient stopped coming to our institution with no clearreason Table 1

3 Discussion

We described a case of ldquoProtractedrdquo HBS in a female patientfollowing parathyroidectomy for primary hyperparathy-roidism caused by an atypical parathyroid adenomaThe pri-mary hyperparathyroidism remainedundiagnosed for at least4 years and was complicated by the occurrence of browntumors severe osteoporosis nephrocalcinosis and shortstature

Postoperative hypocalcemia following parathyroidec-tomy could be associated with numerous causes Some com-mon causes are transient hypoparathyroidism due to exten-sive surgical removal of parathyroid glands disruption ofblood supply to remnant parathyroid glands radical neckexploration and major remineralization of bone such asin HBS [2 7 15] The main features that favor the diag-nosis of hypoparathyroidism versus HBS are the extent ofsurgery bilateral neck exploration or prior neck surgery Alsohypoparathyroidism usually presents with hypocalcemia andhyperphosphatemia [2 16] HBS is associated with high andlong term requirements of calcium and vitamin D supple-mentation with normal or high PTH levels [2 7]

The lack of consensus for the definition of HBS hindersthe comparison of reported cases validation of risk factors

determination of severity and prognosis predictors proposalof prophylaxis regimens and delineation of treatment goalsas well as resolution criteria [4 7]

Clinical and laboratory risk factors for HBS are older ageweight and volume of resected parathyroid glands elevatedalkaline phosphatase evidence of significant bone diseaseand blood urea nitrogen [2 7] The length of hospitalizationhas been associated with severity of hypocalcemia [2]

In order to prevent HBS some authors suggest treatmentwith bisphosphonates in primary [17] and secondary hyper-parathyroidism [18] however this approach may delay boneremodeling [19]

The lesion resected from our patient was compatiblewith atypical adenoma because it presented capsule invasionwithout trespassing its boundaries the rest of the surgicalpiece was analyzed finding normal thyroid and lymph nodeswithout invasion According to the World Health Orga-nization criteria (WHO 2004) [20] an atypical adenomarefers to large glands with either excess mitotic cells andtumor capsule invasion without exceeding its boundaries orwith marked fibrotic divisions pattern It is associated withneither spontaneous tumor necrosis nor vascular invasion tosurrounding tissues [21 22] These pathology characteristicshave been usually associated with a benign course in termsof survival Parathyroid carcinoma specimens have beenassociated with the development of HBS [8 10ndash12]

Due to the sporadic nature severity of symptoms andyoung age at presentation genetic abnormalities could be sus-pected as the cause of this clinical presentation such as gainof function of protooncogenes (e gr cyclinD1PRAD1) orinactivation of tumor suppressor genes (e grMEN1 multipleendocrine neoplasia 1)

Primary hyperparathyroidism (PHPT) is the most com-mon feature of MEN1 and presents in approximately 90of MEN1 patients [23 24] The PHPT main manifestationsreported as part of MEN1 syndrome are earlier age atonset (20 to 25 yrs versus 55 yrs) demineralization andorrecurrent kidney stones [24] findings consistent with the pre-sentation of our patient Normal laboratory analysis ruled outfunctional pituitary adenoma at this time however she willcontinue to be under close observation

Since the patient did not refer to any symptomatology forthe suspicion of a functional pancreaticgastrointestinal (GI)


Calcium (mgdL)

4

6

8

10

12

14

16

4

6

8

10

12

14

16Calcium (mgdL)

(a)

0

1

2

3

4

5Phosphate (mgdL)

0

1

2

3

4

5Phosphate (mgdL)

(b)

005

115

225

3

Year

(01)

3 4Ye

ar (0

2) 1 2 3 4

Year

(03)

1 2 3 4Ye

ar (0

4) 1 2 3 4

Year

(05)

1 2

Magnesium (mgdL)

005

115

225

3

Mon

th (0

1) 1 2 3 3

Mon

th (0

2) 2 3 4M

onth

(03) 2 3 4

Mon

th (0

4) 2 3 4

Magnesium (mgdL)

(c)

Figure 4 (a) Corrected serum calcium during hospitalization and as outpatient (b) Serum phosphate values during hospitalization and asoutpatient (c) Serum magnesium values during hospitalization and as outpatient lowastGray area represents reference values lowastlowastVertical dottedline represents treatment beginning which continued beyond last medical assessment at our institution

adenoma no additional biochemical analyses were carriedout No apparent pancreatic tumors were found on theabdominal CT

Clinical manifestations of hypocalcemia in HBS rangefrom relative benign symptoms such as weakness headacheparesthesias ileus malabsorption and muscle cramps to lifethreatening features such as arrhythmias seizures laryngealstridor tetany and overt severe heart failure [4 7 25] Ourpatient presented mainly musculoskeletal manifestations

In patients withHBS serum electrolytes such as calciumphosphate and magnesium should be cautiously monitoredover the first postoperative hours and days as severe elec-trolytes disturbances may develop [2 3] During hospitaliza-tion the patient required up to 1289mg of elemental calciumIV per day or 429mgkg of elemental calcium IV Treatmentof hypocalcemia is based on oral and intravenous calcium

replacement Reported daily requirements of calcium inpatients with severe hypocalcemia range from 6 to 16 g ofelemental calcium per day [7 10 26ndash28]

The preferred calcium administration route depends onsigns and symptoms severity promptness of the onset ofman-ifestations and serum calcium levels [29 30] Oral calciumsupplementation could be reasonably used in patients withmild symptoms and serum calcium concentrations greaterthan 75mgdL Intravenous treatment is required for patientswith calcium below this level or prolonged QTc interval onelectrocardiogram and may be necessary for those cases whoare currently unable to swallow or absorb oral calcium [30ndash32]

Intravenous calcium gluconate is preferred over calciumchloride due to its lower association with local irritationFor acute hypocalcemia management one or two 10mL


ampoules of 10 calcium gluconate (10mL of a 10 solution= 93mg elemental Ca or 1 ampule) should be diluted in 50ndash100mL of 5 dextrose or saline in order to infuse it over 10minutes [10 31 33] After the patient is stable a calcium infu-sion is continued adding 10 ampoules of calcium gluconate(100mL of 10 calcium gluconate) to 1000mL normal salineor 5 dextrose making up a solution containing 1mgmL ofelemental calcium [33] Typical patient requirements are 05to 15mgkg of elemental calcium per hour [30] Throughouthospitalization the patient required up to 431136mg ofelemental calcium orally per day (equivalent to 108 tablets of1 g of calcium carbonate each tablet contains approximately400mg of elemental calcium)

In HBS once the hyperparathyroid state is resolved itis important to assess serum magnesium and phosphate cir-culating concentrations Significant hypomagnesaemia andhypophosphatemia may develop and perpetuate hypocal-cemia [34 35] Even though mild hypomagnesaemia habit-ually is asymptomatic chronic deficiency may be associ-ated with diverse comorbid situations such as arrhythmiashypertension and an increase in progression of kidneydisease [34] Magnesium levels after parathyroidectomy maydecrease secondary to increased bonemineralization causinga lower PTH secretion and a relative tissue specific resistanceincreasing risk of severe hypocalcemia Therefore magne-sium should be also supplemented [36]

Hypophosphatemia inHBS is probably due to an increasein bone uptake to facilitate matrix remineralization [6]The administration of phosphate in patients with HBS isgenerally avoided because phosphate can precipitate withcalcium decreasing even further the circulating calciumconcentration Phosphate administration is reserved to thosepatients with less than 10mgdL and severe symptoms suchasmuscle weakness or heart failure [5] Phosphate availabilityincreases secondary to the intestinal action of vitamin D

HBS duration has been defined as the time taken to rem-ineralize the skeleton andor cessation of additional calciumsupplementation [7] evidenced by normalization of boneturnover markers healing of radiological features of osteitisfibrosa cystica and brown tumours and significant gain inbone mass Due to the lack of consensus on definitions forHBS length we take into account two of the most cited termsfound in HBS related literature bone mineral density (BMD)recovery and calcium supplementation length

Considering HBS resolution with BMD normalizationcriteria HBS lasted from 45 to 16 months with a median of10 months [2 13 37ndash40] (Table 3) Calcium replenishmenthas been reported throughout 05 months to 12 monthswith a median of 51 months [3 10 13 26 41 42] Usingthis information HBS lasts between 10 and 12 months Wetherefore propose the term of ldquoProtracted Hungry BoneSyndromerdquo to refer to those cases with a particularly longrecovery taking more than one year

In a case series of patients with HBS parathyroidectomyimproved femoral neck bone mineral density (BMD) scoresfrom 35 to 131 in 1 year after surgery considering basal BMDvalues ranging from 0234 to 0564 gcm2 and 1 year follow-up values of 0541ndash0942 gcm2 [43] The significant recovery

Table 3

Time to reach normalbone density values

Time required ofcalcium replenishment References

45 months mdash [2]mdash 5 months [41]8 months mdash [37]mdash 52 months [26]mdash 6 months [10]16 months 3 months [13]

05 months [3]12 months(i) 8 months(ii) 12 months(iii) 12 months

[7][38][39][40]

mdash 12 months [42]Median (months) 10 Median (months) 51 mdash

from baseline pathologic findings to the value above normalfound in our patient is consistent with previously reportedBMDrecovery (Table 3) Bone densitometrieswere only doneat hospital admission and three years after surgery as outpa-tient (Table 2) The factors that contribute to this impressiveBMD improvement in our casewere the resolution of primaryhyperparathyroidism and the high amounts of calcium andvitamin D administered for over 42 months to treat the HBS

To the best of our knowledge the case presented here isone of the longest HBS reported In spite of the HBS criteriadescribed that requires recovery of bone remineralizationwe believe that our patient still has HBS based on the factthat she continues with oral calcium and magnesium supple-mentation to maintain normal serum levels normal circulat-ing vitamin D and normal high PTH levels

4 Conclusion

HBS is a consequence of hyperparathyroidism followingparathyroidectomy It is an infrequent cause of hypocalcemiahypophosphatemia and hypomagnesemia that requires ade-quate therapy to avoid complications in the acute and chronicscenarios We propose the term of ldquoProtracted Hungry BoneSyndromerdquo to refer to those cases with a particularly pro-longed course of recovery that takes more than one year

Conflict of Interests

There was not any financial interest reported by the authorsnor any conflict of interests

Authorsrsquo Contribution

Oscar Alfredo Juarez-Leon and Miguel Angel Gomez-Samano contributed equally to this work


Acknowledgments

Oscar Alfredo Juarez-Leon wants to acknowledge GabrielJuarez and Guadalupe Leon for their support Miguel AngelGomez-Samano wants to acknowledge Luz del CarmenAbascal Olascoaga for her support

References

[1] ldquoThe parathyroid glands and metabolic bone diseaserdquo UlsterMedical Journal vol 19 no 1 pp 130ndash131 1950

[2] A R Brasier and S R Nussbaum ldquoHungry bone syndromeclinical and biochemical predictors of its occurrence afterparathyroid surgeryrdquoTheAmerican Journal of Medicine vol 84no 4 pp 654ndash660 1988

[3] J Latus M Roesel P Fritz et al ldquoIncidence of and riskfactors for hungry bone syndrome in 84 patientswith secondaryhyperparathyroidismrdquo International Journal of Nephrology andRenovascular Disease vol 6 pp 131ndash137 2013

[4] M Goldfarb S S Gondek S M Lim J C Farra V Nose and JI Lew ldquoPostoperative hungry bone syndrome in patients withsecondary hyperparathyroidism of renal originrdquoWorld Journalof Surgery vol 36 no 6 pp 1314ndash1319 2012

[5] M Filopanti S Corbetta A M Barbieri and A Spada ldquoPhar-macology of the calcium sensing receptorrdquo Clinical Cases inMineral and Bone Metabolism vol 10 no 3 pp 162ndash165 2013

[6] R Dunlay and K Hruska ldquoPTH receptor coupling to phospho-lipase C is an alternate pathway of signal transduction in boneand kidneyrdquo The American Journal of PhysiologymdashRenal Fluidand Electrolyte Physiology vol 258 no 2 pp F223ndashF231 1990

[7] J E Witteveen S van Thiel J A Romijn and N A HamdyldquoHungry bone syndrome still a challenge in the post-operativemanagement of primary hyperparathyroidism a systematicreview of the literaturerdquo European Journal of EndocrinologyEuropean Federation of Endocrine Societies vol 168 no 3 ppR45ndashR53 2013

[8] R Varma Y J Kim K Garjian and D Barank ldquoHyperparathy-roidism and hungry bone syndrome revisitedrdquo Clinical NuclearMedicine vol 39 no 8 pp 704ndash706 2014

[9] R K CrowleyM Kilbane T F J KingMMorrinM OrsquoKeaneand M J McKenna ldquoHungry bone syndrome and normalisa-tion of renal phosphorus threshold after total parathyroidec-tomy for tertiary hyperparathyroidism in X-linked hypophos-phataemia a case reportrdquo Journal of Medical Case Reports vol8 article 84 2014

[10] M S Rathi R Ajjan and S M Orme ldquoA case of parathyroidcarcinoma with severe hungry bone syndrome and review ofliteraturerdquo Experimental and Clinical Endocrinology ampDiabetesvol 116 no 8 pp 487ndash490 2008

[11] M N Ohe R O Santos F Hojaij et al ldquoParathyroid car-cinoma and hungry bone syndromerdquo Arquivos Brasileiros deEndocrinologia amp Metabologia vol 57 no 1 pp 79ndash86 2013

[12] K-M Kim J-B Park K-S Bae and S-J Kang ldquoHungrybone syndrome after parathyroidectomyof aminimally invasiveparathyroid carcinomardquo Journal of the Korean Surgical Societyvol 81 no 5 pp 344ndash349 2011

[13] S Tachibana S Sato T Yokoi et al ldquoSevere hypocalcemiacomplicated by postsurgical hypoparathyroidism and hungrybone syndrome in a patient with primary hyperparathyroidismGravesrsquo disease and acromegalyrdquo Internal Medicine vol 51 no14 pp 1869ndash1873 2012

[14] S A Vogelgesang and J M McMillin ldquoHypocalcemia associ-ated with estrogen therapy for metastatic adenocarcinoma ofthe prostaterdquo The Journal of Urology vol 140 no 5 pp 1025ndash1027 1988

[15] D Shoback ldquoHypoparathyroidismrdquoTheNewEngland Journal ofMedicine vol 359 no 4 pp 391ndash403 2008

[16] J P Bilezikian A Khan J T Potts Jr et al ldquoHypoparathy-roidism in the adult epidemiology diagnosis pathophysiologytarget-organ involvement treatment and challenges for futureresearchrdquo Journal of Bone and Mineral Research vol 26 no 10pp 2317ndash2337 2011

[17] I-T Lee W H-H Sheu S-T Tu S-W Kuo and D Pei ldquoBis-phosphonate pretreatment attenuates hungry bone syndromepostoperatively in subjects with primary hyperparathyroidismrdquoJournal of Bone and Mineral Metabolism vol 24 no 3 pp 255ndash258 2006

[18] A Davenport and M P Stearns ldquoAdministration of pamidron-ate helps prevent immediate postparathyroidectomy hungrybone syndromerdquo Nephrology vol 12 no 4 pp 386ndash390 2007

[19] M Coco D Glicklich M C Faugere et al ldquoPrevention of boneloss in renal transplant recipients a prospective randomizedtrial of intravenous pamidronaterdquo Journal of the AmericanSociety of Nephrology vol 14 no 10 pp 2669ndash2676 2003

[20] R A DeLellis Pathology and Genetics of Tumours of EndocrineOrgans IARC Lyon France 2004

[21] Z W Baloch and V A LiVolsi ldquoPathology of the parathyroidglands in hyperparathyroidismrdquo Seminars in Diagnostic Pathol-ogy vol 30 no 3 pp 165ndash177 2013

[22] G G Fernandez-Ranvier E Khanafshar K Jensen et al ldquoPara-thyroid carcinoma atypical parathyroid adenoma or parathy-romatosisrdquo Cancer vol 110 no 2 pp 255ndash264 2007

[23] R V Thakker P J Newey G V Walls et al ldquoClinical practiceguidelines formultiple endocrine neoplasia type 1 (MEN1)rdquoTheJournal of Clinical Endocrinology and Metabolism vol 97 no 9pp 2990ndash3011 2012

[24] P Grzegorz C Jerzy and W Andrzej ldquoPrimary hyperparathy-roidism in patients with multiple endocrine neoplasia type 1rdquoInternational Journal of Endocrinology vol 2010 Article ID928383 6 pages 2010

[25] E Mallet ldquoHypocalcemia clinical signs and mechanismsrdquoArchives de Pediatrie vol 15 no 5 pp 642ndash644 2008

[26] HDemirci E Suyani A Karakoc et al ldquoA longstanding hungrybone syndromerdquo The Endocrinologist vol 17 no 1 pp 10ndash122007

[27] O Laitinen ldquoBone calcium and hydroxyproline metabolismin hyperparathyroidism and after removal of parathyroid ade-nomardquo Acta Medica Scandinavica vol 202 no 1-2 pp 39ndash421977

[28] S M Corsello R M Paragliola P Locantore et al ldquoPost-surgery severe hypocalcemia in primary hyperparathyroidismpreoperatively treated with zoledronic acidrdquo Hormones vol 9no 4 pp 338ndash342 2010

[29] J F Tohme and J P Bilezikian ldquoHypocalcemic emergenciesrdquoEndocrinology andMetabolism Clinics of North America vol 22no 2 pp 363ndash375 1993

[30] J Fong and A Khan ldquoHypocalcemia updates in diagnosisand management for primary carerdquo Canadian Family PhysicianMedecin de Famille Canadien vol 58 no 2 pp 158ndash162 2012

[31] M S Cooper and N J Gittoes ldquoDiagnosis and management ofhypocalcaemiardquoThe British Medical Journal vol 336 no 7656pp 1298ndash1302 2008


[32] J-J Body and R Bouillon ldquoEmergencies of calcium homeosta-sisrdquo Reviews in Endocrine amp Metabolic Disorders vol 4 no 2pp 167ndash175 2003

[33] D Shoback ldquoHypocalcemia definition etiology pathogenesisdiagnosis and managementrdquo in Primer on the Metabolic BoneDiseases and Disorders of Mineral Metabolism chapter 68 JohnWiley amp Sons Hoboken NJ USA 2009

[34] J H F de Baaij J G J Hoenderop and R J M BindelsldquoMagnesium in man implications for health and diseaserdquoPhysiological Reviews vol 95 no 1 pp 1ndash46 2015

[35] FMHannan and R VThakker ldquoInvestigating hypocalcaemiardquoBritishMedical Journal vol 346 no 7911 Article ID f2213 2013

[36] Z S Agus ldquoHypomagnesemiardquo Journal of the American Societyof Nephrology vol 10 no 7 pp 1616ndash1622 1999

[37] F Ghanaat and J A Tayek ldquoHungry bone syndrome a casereport and review of the literaturerdquo Nutrition Research vol 24no 8 pp 633ndash638 2004

[38] K Natsui K Tanaka M Suda et al ldquoOxyphil parathyroidadenoma associated with primary hyperparathyroidism andmarked post-operative hungry bone syndromerdquo Internal Medi-cine vol 35 no 7 pp 545ndash549 1996

[39] T Y Yong and J Y Z Li ldquoMediastinal parathyroid carcinomapresenting with severe skeletal manifestationsrdquo Journal of Boneand Mineral Metabolism vol 28 no 5 pp 591ndash594 2010

[40] T Franca L Griz J Pinho et al ldquoBisphosphonates can reducebone hunger after parathyroidectomy in patients with pri-mary hyperparathyroidism and osteitis fibrosa cysticardquo RevistaBrasileira de Reumatologia vol 51 no 2 pp 131ndash137 2011

[41] C Campusano and J Lopez ldquoComplete recovery of hungrybone syndrome using intravenous calcium infusion Report ofone caserdquo Revista Medica de Chile vol 131 no 7 pp 779ndash7842003

[42] G Ghilardi and L De Pasquale ldquoHungry bone syndromeafter parathyroidectomy for primary hyperthyroidismrdquo SurgeryCurrent Research vol 4 article 168 2014

[43] T C P T de Franca L Griz J Pinho et al ldquoBisphosphonatescan reduce bone hunger after parathyroidectomy in patientswith primary hyperparathyroidism and osteitis fibrosa cysticardquoRevista Brasileira de Reumatologia vol 51 no 2 pp 131ndash1372011

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Table 1 Laboratory findings at hospital admission and at last outpatient follow-up visit

Hospitalization[February 2010]

Follow-up[November 2013] Reference values

Serum calcium [mgdL] 121 89 86ndash99Corrected serum calcium [mgdL]lowast 126 79Serum phosphate [mgdL] 27 3 27ndash45Serum magnesium [mgdL] 13 2 19ndash27Serum albumin [gdL] 34 52 35ndash57Serum creatinine [mgdL] 483 105 042ndash109Creatinine clearance [mlmin173m2] 12 76 ge90PTH [pgmL] 2551 917 12ndash8825-OH vitamin D [ngmL] 13 259 30ndash100Alkaline phosphatase [IUL] 4410 126 34ndash104Urinary calcium [mgday] 213 22 100ndash300Urinary phosphorus [mgday] 413 524 lt1000Prolactin [ngmL] 126 mdash 264ndash1313FSH [mIUmL] 44 mdash 385ndash878(follicular phase)

LH [mIUmL] 17 mdash 212ndash1089(follicular phase)

Estradiol [pgmL] 3613 mdash 12ndash40(follicular phase)

T3 [nmolL] 178 mdash 064ndash181T4 [nmolL] 6933 mdash 66ndash181TSH [120583UImL] 185 mdash 03ndash5Thyroglobulin [ngmL] 57 mdash 0ndash368ACTH [pgmL] 19 mdash 10ndash100Morning cortisol [120583gdL] 1576 67ndash226PTH parathyroid hormonelowastCorrected calcium with albumin using the following formula Ca2+corrected = Ca2+measured + 08 times [4 minus albuminmeasured]

serum calcium levels Treatment of primary hyperparathy-roidism often requires surgical resection of an adenomacausing a sudden halt in bone turnover Consequently amarked depletion of serum circulating calcium phosphateand magnesium is seen due to bone remineralization [2]

The most common etiologies associated with HBS aresecondary and primary hyperparathyroidism [3 7 8] Otherless frequent causes are parathyroid carcinoma drugs mul-tiple endocrine neoplasia and metastatic prostate cancer [9ndash14]

Here we present a clinical case of an unusual long-lasting HBS developed in a female patient with primaryhyperparathyroidism after surgical treatment of an atypicaladenoma

2 Case Presentation

An 18-year-old previously healthy woman presented at ourinstitution after a four-year history of hyporexia polydip-sia weight loss growth retardation and poor academicperformance One month prior to presentation outpatientlaboratory analysis revealed increased serum calcium andparathyroid hormone (PTH) She did not have any othersignificant personal or family history

She was admitted to our hospital in February 2010 Onphysical examination her height was 140m and weight was

30 kg Her vital signs were within normal limits She pre-sented with a marked cervical kyphosis

Relevant laboratory results showed hypercalcemia(1336mgdL normal 86ndash99mgdL) elevated PTH (2551 pgmL normal 12ndash88 pgmL) elevated alkaline phosphataselevel (4410 IUL normal 34ndash104 IUL) hypercalciuria (uri-nary calcium of 213mg24H normal 100ndash250mg24H) lowcreatinine clearance (2584mLmin173m2 normalge90mLmin173m2) and low 25[OH]D

3circulating level (13 ngmL

normal 30ndash100 ngmL) The laboratory findings at hospitaladmission and last follow-up visit are summarized in Table 1Biochemical approach was further completed with prolactin126 ngmL FSH 44mIUmL LH 17mIUmL estradiol3613 pgmL T3 178 nmolL T4 6933 nmolL TSH 185 120583UImL thyroglobulin 57 ngmL ACTH 19 pgmL andmorningcortisol 1576 120583gdL all within normal limits

Skeletal X-rays showed skull with ldquosalt and pepperrdquolesions vertebral compression fractures brown tumorswithin the left humerus and profuse calcifications within thepancreas and kidneys (Figure 1) The patient did not referto abdominal pain nor any symptomatology related toendocrine and exocrine pancreatic insufficiency The elec-trocardiogram was unremarkable Abdominal ultrasoundrevealed kidney stones causing bilateral dilation of the renalpelvis Neck ultrasonography showed microcalcificationswithin a large echogenic mass posterior to the right lobe of


(a) (b)


(a) (b)










20min 120min

(a)

20min 120min

(b)




3 Discussion












Calcium (mgdL)

4

6

8

10

12

14

16

4

6

8

10

12

14

16Calcium (mgdL)

(a)

0

1

2

3

4

5Phosphate (mgdL)

0

1

2

3

4

5Phosphate (mgdL)

(b)

005

115

225

3

Year

(01)

3 4Ye

ar (0

2) 1 2 3 4

Year

(03)

1 2 3 4Ye

ar (0

4) 1 2 3 4

Year

(05)

1 2

Magnesium (mgdL)

005

115

225

3

Mon

th (0

1) 1 2 3 3

Mon

th (0

2) 2 3 4M

onth

(03) 2 3 4

Mon

th (0

4) 2 3 4

Magnesium (mgdL)

(c)















Table 3





[7][38][39][40]




4 Conclusion







Acknowledgments


References


















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















(a) (b)


(a) (b)










20min 120min

(a)

20min 120min

(b)




3 Discussion












Calcium (mgdL)

4

6

8

10

12

14

16

4

6

8

10

12

14

16Calcium (mgdL)

(a)

0

1

2

3

4

5Phosphate (mgdL)

0

1

2

3

4

5Phosphate (mgdL)

(b)

005

115

225

3

Year

(01)

3 4Ye

ar (0

2) 1 2 3 4

Year

(03)

1 2 3 4Ye

ar (0

4) 1 2 3 4

Year

(05)

1 2

Magnesium (mgdL)

005

115

225

3

Mon

th (0

1) 1 2 3 3

Mon

th (0

2) 2 3 4M

onth

(03) 2 3 4

Mon

th (0

4) 2 3 4

Magnesium (mgdL)

(c)















Table 3





[7][38][39][40]




4 Conclusion







Acknowledgments


References


















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















20min 120min

(a)

20min 120min

(b)




3 Discussion












Calcium (mgdL)

4

6

8

10

12

14

16

4

6

8

10

12

14

16Calcium (mgdL)

(a)

0

1

2

3

4

5Phosphate (mgdL)

0

1

2

3

4

5Phosphate (mgdL)

(b)

005

115

225

3

Year

(01)

3 4Ye

ar (0

2) 1 2 3 4

Year

(03)

1 2 3 4Ye

ar (0

4) 1 2 3 4

Year

(05)

1 2

Magnesium (mgdL)

005

115

225

3

Mon

th (0

1) 1 2 3 3

Mon

th (0

2) 2 3 4M

onth

(03) 2 3 4

Mon

th (0

4) 2 3 4

Magnesium (mgdL)

(c)















Table 3





[7][38][39][40]




4 Conclusion







Acknowledgments


References


















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Calcium (mgdL)

4

6

8

10

12

14

16

4

6

8

10

12

14

16Calcium (mgdL)

(a)

0

1

2

3

4

5Phosphate (mgdL)

0

1

2

3

4

5Phosphate (mgdL)

(b)

005

115

225

3

Year

(01)

3 4Ye

ar (0

2) 1 2 3 4

Year

(03)

1 2 3 4Ye

ar (0

4) 1 2 3 4

Year

(05)

1 2

Magnesium (mgdL)

005

115

225

3

Mon

th (0

1) 1 2 3 3

Mon

th (0

2) 2 3 4M

onth

(03) 2 3 4

Mon

th (0

4) 2 3 4

Magnesium (mgdL)

(c)















Table 3





[7][38][39][40]




4 Conclusion







Acknowledgments


References


















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of























Table 3





[7][38][39][40]




4 Conclusion







Acknowledgments


References


















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Acknowledgments


References


















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















atypical parathyroid adenoma complicated with protracted hungry

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