diseases of the parathyroid gland ... -...

SEMMELWEIS UNIVERSITY

2nd Department of Medicine http://semmelweis.hu

DISEASES OF THE PARATHYROID GLAND METABOLIC BONE DISEASES

OSTEOPOROSIS

dr. Judit Tőke

Diseases of the parathyroid gland. Metabolic bone diseases. Osteoporosis dr. Judit Tőke: SEMMELWEIS UN IVERSITY ©

http://semmelweis.hu

Outline

Diseases of the parathyroid gland

Primary hyperparathyroidism

Primary hypoparathyroidism

Metabolic bone diseases

Disorders in Vitamin D action (rickets and osteomalatia)

Secondary hyperparathyroidism in chronic kidney disease

Osteogenesis imperfecta

Paget’s Disease of Bone

Osteoporosis



The last anatomical discovery....

Ivar Sandström, 1852–1889.

Sandström IV: On a new gland in man and several mammals –

glandulae parathyroideae.

Upsala Läk Förenings Förh. 1879–1880;15:441–71 Swedish

That remarkable discovery was made in 1877 at the Anatomical Department in Uppsala. At that time

Sandström was a young medical student, who had worked as an assistant at the department since 1873.

Virchow declined its publication in his journal, because of the length of the paper (30 pages)......

Johansson H: The Uppsala anatomist Ivar Sandström and the parathyroid gland. Ups J Med Sci. 2015 May; 120(2): 72–77



Primary hyperparathyroidism (PHPT)

Prevalence of PHPT:

- North-America: 1/1000

- North-Europe: 3-4/1000

- in the population oldre than 75 years: 20/1000

- women:men=2-3:1

Pathology of parathyroid glands causing PHPT:

- single adenoma (80-85%)

- double adenoma (1-2%)

- hyperplasia (10-15%)

- carcinoma (<1%)

- cyst (1-3%)



Symptoms of PHPT Skeleton: - bone pain

- fractures

- decrease of BMD: osteopenia/osteoporosis

- osteitis fibrosa cystica

Joints: - arthralgy

Muscles: - weakness of proximal muscles

- muscle atrophy

Renal: - renal stones

- nephrocalcinosis

- nephrogene diabetes insipidus

- renal insufficiency

Gastrointestinal: - peptic ulcer

- acute pancreatitis

Psychiatric: - depression

Rare: Hypercalcemic crisis!! Causes: - parathyroid npl. hemorrhage/necrosis

- infection

- exsiccosis



Changes in clinical picture of PHPT

Author Cope Heath Mallette Silverberg

1930-1965 1965-1974 1965-1972 1984-2000

(%) (%) (%) (%)

Renal stones 57 51 37 17

Skeletal symptoms 23 10 14 1.4

Hypercalciuria NA 36 40 39

Asymptomatic 0.6 18 22 80

John P. Bilezikian and Shonni J. Silverberg

Reviews in Endocrine & Metabolic Disorders 2000; 237-245



Diagnosis of PHPT - Laboratorical investigations

elevated or normal PTH concentration > 63 pg/ml

AND

hypercalcaemia: total serum calcium corrected to albumin > 2.63 mmol/l

ionized serum calcium > 1.25 mmol/l

Diagnosis of PHPT – Radiological investigations

CT, MRI: sensitivity:50-70%

Ultrasound: sensitivity: 40-80%

99mTc-sestamibi substraction isotope: sensitivity for single adenoma: 90%

for the diagnosis of ectopic parathyroid tissue

N.B:in the absence of conditions mimicking PHPT (thiazide diuretics or lithium)



99mTc-sestaMIBI scan

(MIBI = methoxyisobutylisonitrile)



Indications for surgery for the treatment of PHPT

Khan AA et al: Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus.

Osteoporos Int. 2017 28(1):1-19



Surgery for the treatment of symptomatic PHPT

• Parathyroidectomy (PTx) is the only curative approach to this disease.

• Cure rates following PTx ~ 95 %

• Post-PTX:

• reductions in the risk of all fractures

• decrease of renal stone risk

• IOPTH: intraoperative PTH - measurement with a rapid assay is of value in confirming

adequate resection of abnormal parathyroid tissue and increases surgical success rates

• Persistent PHPT = development of hypercalcemia within 6 months of PTx

If there is a contraindication for surgery:

• Vitamin D supplementation – goal: serum 25OHD > 50nmol/l

• antiresorptive therapy (bisphosphonates) – in patients with osteoporosis

• cinacalcet



Management of asymptomatic PHPT

Bilezikian et al. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.

J Clin Endocrinol Metab, 2014, Aug 27

Monitoring appears to be a safe option for possibly up to 8 to 10 years for patients with

asymptomatic PHPT



Familial syndromes with PHPT

Multiplex endocrine neoplasia type 1 MEN1

-prevalence: 30-40/million

-2% of all cases

Multiplex endocrine neoplasia type 2A MEN2A

-prevalence: 40/million

Hyperparathyreosis-jaw tumor syndrome HPT-JT

Familial isolated primary hyperparathyroidism FIHP

Familial hypocalciuric hypercalcemia FHH

More than one parathyroid gland are affected in 15% of all cases and half of them is a

part of a familial syndrome (5-8% of all cases)



Iatrogen:

neck irradiation, neck surgery (thyroid!!!)

Infiltrativ / destructive diseases:

haemochromatosis, sarcoidosis, Wilson-disease, amyloidosis

Genetic disease:

DiGeorge-syndrome

APS-1 syndrome:

- Hypoparathyroidism diabetes mellitus type 1

- Addison-disease autoimmune thyroid disease

- Mucocutan candidiasis chronic active hepatitis

alopecia

vitiligo

Primary hypoparathyroidism



Definition of hypocalcemia:

Serum calcium < 2.23 mmol/l, Ionic calcium < 1.05 mmol/l

Symptoms of hypocalcemia:

It depends on:

- the rate of the development

- the severity of the hypocalcemia

- and the elapsed time from the begining

* neuromuscular : enhanced excitation in neurons

paresthesia, tetania, laryngospasmus, bronchospasmus

* neurol-psych : intracran. calcification (basal ggl, cortex), change in

personality, parkinsonism, psychosis

* skin : dry skin, atopic ekzema, caries

* GI : dysphagia, abdominal pain, colica in bile ducts

* pulmonary : dyspnoe, wheezing

* cardiovascular : longer QT-interval, congestive heart failure,

cardiomyopathy



Disorders in Vitamin D action

Rickets:

defects in mineralisation of bone and cartilage during childhood

Osteomalatia:

defects in mineralisation of bone in adulthood

Serum levels 24h urinary calcium excretion

Etiology Calcium Phosphorous iPTH Bone specific ALP

Hypocalcemic e.g. vitamin D deficiency

Low to low normal

Low Elevated Elevated Low

Hypophosphatemic e.g. X-linked hypophosphatemia

Normal Low Normal to low normal

Elevated Low to elevated

No abnormality in mineral homeostasis e.g. hypophosphatasia

Normal Normal Normal Low Normal

From: Disorders in Vitamin D Action

Endotext [Internet].

De Groot LJ, Chrousos G, Dungan K, et al., editors.

South Dartmouth (MA): MDText.com, Inc.; 2000-.



Rickets

Clinical features: weakness, bone pain, bone deformity, fracture

0-1 years:

craniotabes, widening of the wrists, rachitic rosary, deformed rib cage

> 2 years:

bow legs (genu varum) or knock-knee (genu valgum),

widening of the end of long bones



Osteomalatia

Clinical features: bone pain or low back pain, muscle weakness, hypotonia

acute fracture of the long bones, pubic ramii, ribs, or spine

Looser-zones (pseudofractures)

biconcave vertebrae

From: Disorders in Vitamin D Action

Endotext [Internet].

De Groot LJ, Chrousos G, Dungan K, et al., editors.

South Dartmouth (MA): MDText.com, Inc.; 2000-.



Michael P.Whyte, Rajesh V.Thakker: Rickets and osteomalacia. Medicine 33 (12) p70-74, 2005



Secondary hyperparathyroidism in chronic kidney disease

Kobama H: FGF23-parathyroid interaction: implications in chronic kidney disease. Kidney Int. 77(4):292-8, 2010

Clinical features: usually silent disease

• severe osteitis fibrosa

• clinical signs of hyperCa, hyperP

Treatment:

• Vitamin D: active vitamin D – calcitriol!

• Calcimimetics

• Phosphate binders

• Oral phosphate restriction



Osteogenesis imperfecta

Clinically and genetically heterogeneous group of heritable disorders of connective tissue

(collagen related disorder)

85%: AD mutations in the genes that encode type I collagen, COL1A1 and COL1A2

Clinical features:

bone fragility, bone deformity, growth deficiency

macrocephaly, blue sclerae, dentinogenesis imperfecta, hearing loss, neurological defects

(macrocephaly and basilar invagination) cardiopulmonary complications

Treatment:

physical rehabilitation, supplemented with orthopedic intervention as needed

oral bisphosphonates

gene therapy?



Paget’s Disease of Bone

Clinical features:

• skeletal deformity which evolves over many years: skull and lower extremities.

• pathological fractures in the femurs.

• pain of skeletal, joint, neurologic or muscle origin.

• The radiologic features:

1. localized area of osteolysis which advances very slowly

2. the lesion becomes osteosclerotic

3. entire bone is affected the entire lesion is sclerotic with areas of osteolysis

Treatment:

iv. zoledronate

surgery: lower extremity joint replacement

correction of deformities of the lower extremity.



Osteoporosis

Osteoporosis is a systemic, progressive disease.

Decreased bone mass, altered microarchitecture --- fragile bones which are at an

increased risk for fractures.



Diagnosis 1. Fracture risk assessment



Diagnosis 2. Finding secondary causes



Osteoporosis prevention

1. Physical activity

2. Optimal diet with 1000-1200 mg calcium daily

3. Optimal vitaminD – with supplementation (800-2000 IU cholecalciferol daily), if needed

4. Discontinuation of smoking



Treatment I: Antiresorptive mediactaions

Bisphosphonates:

• Alendronate oral; prevents vertebral, non-vertebral-, hip fractures in postmenopausal women

• Risedronate oral; prevents vertebral, non-vertebral-, hip fractures in postmenopausal women

• Ibandronate oral or iv. ; prevents vertebral fractures

• Zoledronate iv; prevents vertebral, non-vertebral-, hip fractures in postmenopausal women

Caution: in high doses, increases the risk of osteonecrosis of jaw

Raloxifene oral; prevents vertebral fractures in postmenopausal women

Caution: may increases the risk of thromboembolic disease and stroke

Denosumab sc; prevents vertebral, non-vertebral-, hip fractures in postmenopausal women

Calcitonin intranasal spray; : Reduces incidence of vertebral fractures in post-menopausal women

Consider as an alternative when other more effective drugs cannot be used

Effective in decreasing acute pain associated with vertebral osteoporotic fractures

Hormone replacement therapy mainly in those women who have symptoms of menopause

Caution: increase the risk of breast carcnoma, thromboembolic disease, ischaemic heart disease (gestagen containing drugs!!)

II. Bone-forming medication

Teriparatide sc; prevents vertebral and non-vertebral fractures in postmenopausal women with severe OP

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