Hyperparathyroidism

Adenoma REF: Blueprints Surgery by Seth J. Karp, James Morris, David I. Soybel Page 85

• Hyperparathyroidism is the most common cause of surgically correctable hypercalcemia.
• Primary hyperparathyroidism is a surgical disease and operation is required for the hyperfunctioning gland (A single hyperfunctioning adenoma accounts for approximately 90% cases)
• Secondary hyperparathyroidism of renal disease is treated medically.
• Tertiary hyperparathyroidism due to autonomous parathyroid hyperplasia occasionally requires surgery.

Ans:C.)Radial border of middle phalanx

The classic features of hyperparathyroidism are subperiosteal resorption, endosteal resorption, and osteopenia.

Subperiosteal bone resorption

• classically affects the radial aspects of the proximal and middle phalanges of the 2nd and 3rd fingers
• medial aspect of tibia, femur, humerus
• lamina dura: floating teeth (not specific)

In chronic kidney disease, hyperphosphatemia and decreased renal production of 1,25-dihydroxycholecalciferol (1,25[OH]2D3) initially produce a decrease in ionized calcium. The parathyroid glands are stimulated (secondary hyperparathyroidism) and may enlarge, becoming autonomous (tertiary hyperparathyroidism).
In osteomalacia and rickets, hypocalcemia acts as stimulus to secondary hyperparathyroidism.

Ref: Shoback D., Sellmeyer D. (2011). Chapter 8. Metabolic Bone Disease. In D.G. Gardner, D. Shoback (Eds), Greenspan’s Basic & Clinical Endocrinology, 9e.

Ans. is ‘d’ i.e., Secondary hyperparathyroidism with chief cell adenoma

o Davidson states “In very small proportion of cases of secondary hyperparathyroidism continuous stimulation of the parathyroid may result in adenoma formation and autonomous PTH secretion. This is known as tertiary

hyperparathyroidism”.

A i.e. Skull; B i.e. Phalanges

Hallmark or characteristic feature of hyperparathyroidism is-subperiosteal Erosion of bone, particularly radial aspect of middle phalynx of middle & index finger.Q

D i.e. Subperiosteal resorption of bone (phalynges)

Very interestingQ friends as all the options are the features of hyperparathyroidism but they are asking about the hallmark or characteristic feature which is ‑

Subperiosteal Erosion of bone, particularly radial aspect of middle phalynx of middle & index finger.Q

Answer is ‘a’ i.e. Parathyroid hyperplasia; ‘b’ i.e. Adenosis; ‘c’ i.e. MEN 1

Hyperparathyrodism is defined as elevated serum PTH due to increased secretion. It is of two types. a) Primary & b) Secondary with a rare third type – c) Tertiary

Primary hyperparathyroidism

• Primary hyperparathyroidism is due to intrinsic abnormality of one or more parathyroid glands:
• Single Adenoma –> 83%
• Multiple Adenomas  —> 6%
• Hyperplasia —> 1%
• Carcinoma —> 1%

[To according to CSDT, may vary in cliff books, but general order is same]

• Adenomas and hyperplasia of the parathyroid usually occur sporadically, but in few cases, they are part of familial syndromes

Familial syndromes associated with Primary Hyperparathyroidism

• MEN type 1-Wermer’s syndrome
• MEN type 2a – Sipple syndrome
• Familial hypocalciuric hypercalcemia

Secondary Hyperparathyroidism

• Sec. hyperparathyroidism is increased secretion of PTH by the parathyroids in response to a lowered serum ionized calcium level
• Causes

-Chronic renal failure (most common cause)

-Malabsorption syndrome

-Vitamin D deficiency

-Medullary carcinoma of thyroid

Tertiary Hyperparathyroidism

Tertiary hyperparathyroidism follows long standing secondary FIPT when the chronically stimulated parathyriod glands act independently of the serum calcium concentration. Autonomous hypersecretion of PTH may persist despite correction of the underlying condition.

Ans. is ‘d’ i.e., All of the above 

Answer is D (Phosphate Binders)

The initial treatment of secondary hyperparathyroidism in renal osteodystrophy is management of high phosphate levels by dietary restriction and the use of Phosphate binders

• The objectives of management are to maintain blood levels of calcium and phosphorous to as close to normal as possible, to prevent or treat established hyperparathyroidism early and to prevent parathyroid hyperplasia.

Phosphate retention begins early in the course of CKD, perhaps as early as in stage 2 and participates in the development of secondary hyperparathyroidism.

Central to the management of high-turnover bone disease is controlling the serum  phosphate levels.

This may be achieved by dietary phosphate restriction or by the use of phosphate binders. 

Phosphate-binder therapy is recommended when serum phosphate concentrations are elevated despite patient compliance with dietary phosphate restriction.

Calcium-based phosphate binders are often recommended as the initial binder therapy.

High Bone Turnover Disease

• Bone turnover (the formation and removal of bone) is increased due to a process called secondary hyperparathyroidism (SHPT).
• Secondary hyperparathyroidism represents a common disorder in patients with CKD.
• It develops as a result of hyperphosphatemia, hypocalcemia and impaired renal vitamin D synthesis with reduction in serum calcitriol levels

Answer is B (Solitary parathyroid adenoma) :

The most common cause of primary hyperparathyroidism is a parathyroid adenoma.

A single/solitary abnormal gland is the cause in approximately 80% of patients – Harrison

The abnormality of the gland is usually a benign neoplasm or ‘adenoma’ and rarely a parathyroid carcinoma

Answer is A (Commonly occurs after thyroidectomy):

Thyroidectomy may lead to hypoparathyroidism and not hyperparathyroidism due to inadvertent removal of the parathyroid glands.

Answer is D (Asymptomatic hypercalcemia)

In view of the above facts from Harrison the best option to consider a ‘subtle presentation’ should probably be `asymptomatic hypercalcemia’

Answer is C (Chronic renal failure):

Conditions leading to decrease in serum calcium levels cause a compensatory increase in secretion of PTH resulting in secondary hyperparathyroidism. Amongst the options provided chronic renal failure is one such cause of secondary hyperparathyroidism.

Primary hyperparathyroidism

• Elevated PTH due to increased PTH secretion from an intrinsic abnormality of one or more parathyroid glands
• This is most commonly due to solitary adenoma involving one gland

Secondary hyperparathyroidism

• Excessive secretion of PTH by parathyroids secondary to a lowered serum ionized calcium
• This is a compensatory hyperplasia of all four glands aimed at correcting lowered serum calcium

Ectopic parathyroid hormone syndrome

• Ectopic PTH syndrome results from the production by several malignant neoplasms of PTH related peptide

Answer is C (Osteoporosis):

Osteoporosis is neither associated with hypocalcaemia nor with secondary Hyperparathyroidism

Answer is A (Osteopetrosis):

Hyperparathyroidism is associated with osteoporosis and not with osteopetrosis.

Answer is C (Decrease in serum calcitonin) :

Serum calcitonin is no marker fir hyperparathyroidism. It antagonizes the actions of parathyroid hormone and may be used as a modality of treatment of hypercalcemia secondary to hyperparathyroidism.

Markers of hyperparathyroidism (↑^ed PTH):

1. Increased serum calcium:

Stimulates Vit D which causes increased absorption of Ca^-H- from gut

Increased calcium reabsorption from tubules

Increases osteoblastic activity in bones and mobilizes calcium from bone into serum.

2. Decreased serum phosphorus:

–  PTH acts on tubules to increase excretion of phosphorus.

3. Increased 24 hr urine calcium:

– Despite increased reabsorption of Ca⁺⁺ in renal tubules urinary calcium is increased owing to increased filtration of calcium in glomerular filtrate.

4. Increased Alkaline phosphatase: –Increased resorption of bone leads to compensatory elevation of osteoblastic activity

5. Radiological changes:

Subperiosteal resorption of phalanges is characteristic (hand X Rays are always advised) Bone resorption i.e. osteitis fibrosa et cystica (brown tumours)

`Salt pepper’ or ‘pepper pot skull’ appearance

– Loss of lamina dura

Answer is B (Low Urinary Calcium):

Primary Hyperparathyroidism is associated with normal or increased urinary calcium levels.

Increased PTH and Increased Serum calcium in association with high levels of urinary calcium suggest a diagnosis of Primary Hyperparathyroidism

Increased PTH and Increased Serum calcium in association with low levels of urinary calcium suggest a diagnosis of Familial Hv^pocalciuric Hv^percalcemia (FHH)

This clearance ratio is calculated from simultaneous fasting serum and urine Ca and creatinine measurements. The urine sample can be from a spot or a 24 h collection. The clearance ratio is calculated as follows:

Urine Ca (mg/24h)x plasma creatinine (mg/dl )/plasma Ca (mg/dL) x urine creatinine (mg/24h)

Ans. A: Hypocalcemia

• Raised serum Calcium with high serum PTH
• Serum alkaline phosphatase – often normal but may be markedly increased in bone disease
• Serum phosphate:

– Decreased in about half of cases

– a Eaised serum phosphate suggests nonparathyroid hypercalcaemia

– a Normal serum phosphate is not diagnostically useful/in case of renal failure

• Urine Ca – increased in most patients
• Metabolic acidosis is reflected by reduced plasma bicarbonate and high plasma chloride
• Bone radiographs – pathognomonic subperiosteal bone resorption of the phalanges; there may be loss of the lamina Jura of the teeth; in severe cases osteitis fibrosa cystica is present.

Ans. C: Adenoma

Hyperparathyroidism causes hypercalcemia through the excessive secretion of parathyroid hormone, usually by an adenoma (benign tumors) of the parathyroid glands (nearly 80%).

Chief cell parathyroid hyperplasia accounts for nearly 15% cases.

Ans. C: Primary hyperparathyroidism

Other conditions associated with hypercalcemia include:

• Cancers, particularly multiple myeloma, breast cancer and lung cancer;
• Excessive levels of vitamin D from vitamins, excessive dietary calcium, or from diseases that may result in excess vitamin D production;
• Immobilization over a long period of time;
• Kidney failure;
• Overactive thyroid (hyperthyroidism) or excessive thyroid hormone intake; and
• Use of certain medications such as thiazide diuretics.
• Endocrine disorders like adrenal insufficiency, pheochromocytoma

Calcitonin is a hypocalcemic hormone.

Ans. Hyperparathyroidism

Ans. Hyperparathyroidism

Ans. is `d’ i.e., Hyperparathyroidism

Ans. is ‘a’ i.e., Hyperparathyroidism

Salt and pepper sign or pepperpot skull of the calvarium refers to multiple tiny well-defined lucencies in the skull vault caused by resorption of trabecular bone in hyperparathyroidism.

There is a loss of definition between the inner and outer tables of the skull and a ground-glass appearance as well as spotty deossification.

Appearance of phalanges as represented by an arrow shown in photograph above demonstrates subperiosteal resorption of phalanges.

Subperiosteal bone resorption is the most consistent and specific finding of hyperparathyroidism and is virtually pathognomonic of the condition.

Ans:D.)Hyperparathyroidism.

In the image:X-ray of the skull showing salt and pepper appearance with multiple punched out lesions: classical of primary hyperparathyroidism. 

Hyperparathyroidism

• It is a disease characterized by excessive secretion of parathyroid hormone.

Function of PTH:

• The main effects of parathyroid hormone are to increase the concentration of plasma calcium by increasing the release of calcium and phosphate from bone matrix, increasing calcium reabsorption by the kidney, and increasing renal production of 1,25-dihydroxyvitamin D-3 (calcitriol), which increases intestinal absorption of calcium. Parathyroid hormone also causes phosphaturia, thereby decreasing serum phosphate levels.

Hyperparathyroidism is usually subdivided into primary, secondary, and tertiary hyperparathyroidism.

Primary hyperparathyroidism

• It is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium homeostasis.
• Cause:
  • Single adenoma(85% of cases), multiple adenomas or hyperplasia in 15% of cases, rarley parathyroid carcinoma.
  • Familial cases can occur either as part of the multiple endocrine neoplasia syndromes (MEN 1 or MEN 2a), hyperparathyroid-jaw tumor (HPT-JT) syndrome, or familial isolated hyperparathyroidism (FIHPT).
• Clinical features:
  • The clinical syndrome of primary hyperparathyroidism can be easily remembered as “Bones, stones, abdominal groans, and psychic moans.”
• Skeletal manifestations include selective cortical bone loss, which is common.
  • In the early clinical description of primary hyperparathyroidism, some patients developed a peculiar type of bone disease known as osteitis fibrosa cystica, characterized by increased generalized osteoclastic bone resorption, particularly involving the phalanges causing subperiosteal resorption, and the skull causing the radiologic appearance known as salt and pepper skull.
  • Salt and pepper sign or pepperpot skull of the calvarium refers to multiple tiny well-defined lucencies in the skull vault caused by resorption of trabecular bone in hyperparathyroidism.
  • There is a loss of definition between the inner and outer tables of the skull and a ground-glass appearance as well as spotty deossification.
• Treatment:
  • Surgical excision of the abnormal parathyroid glands  offers the only permanent, curative treatment for primary hyperparathyroidism.

Secondary hyperparathyroidism

• It is due to physiological (i.e. appropriate) secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels).
• Cause:
  • The most common causes are vitamin D deficiency(caused by lack of sunlight, diet or malabsorption) and chronic kidney failure.
• Clinical Features:
  • Because virtually all patients with renal failure have hyperparathyroidism to some degree, the clinical presentation is often that of renal failure. In patients with secondary hyperparathyroidism due to vitamin D deficiency, the symptoms are mainly due to the vitamin deficiency (eg, osteomalacia with increased fracture risk, myopathy.
  • The bone disease in secondary hyperparathyroidism caused by renal failure is termed renal osteodystrophy.
• Treatment
  • It must be directed at the underlying cause of this (usually vitamin D deficiency or chronic kidney failure).

Tertiary hyperparathyroidism

• It is seen in patients with long-term secondary hyperparathyroidism, which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with chronic renal failure and is an autonomous activity.

Ans.:C.)Thyroid malignancy

Hyperparathyroidism

Pathology

• Increased levels of the PTH lead to increased osteoclastic activity. The resultant bone resorption produces cortical thinning (subperiosteal resorption) and osteopaenia.

Subtypes

• primary hyperparathyroidism
  • parathyroid adenoma (~80%)
  • multiple parathyroid adenomas (4%)
  • parathyroid hyperplasia (10-15%)
  • parathyroid carcinoma (1-5%)
• secondary hyperparathyroidism
  • caused by chronic hypocalcaemia with renal osteodystrophy being the most common cause (others include malnutrition, vitamin D deficiency)
  • results in parathyroid hyperplasia
• tertiary hyperparathyroidism
  • autonomous parathyroid adenoma caused by the chronic overstimulation of hyperplastic glands in renal insufficiency

Ans. b. Hyperparathyroidism

Ans. is ‘a’ i.e., Primary hyperparathyroidism

• The initial osseous lesions associated with primary hyperparathyroidism show merely a decrease in bone density. The full blown osseous manifestations have been referred to as osteitis fibrosa cystica (OFC) or Recklinghausen’s disease.

Primary hyperparathvroidism (Osteitis fibrosa cystica, von recklinghausen’s disease)

• Primary hyperparathyroidism refers to increased parathormone secretion due to primary pathology in parathyroid gland. Primary adenoma is the most common cause of primary hyperparathyroidism. Rise in parathormone causes increased osteoclastic activity, which resorbs the bone. Consequently, there is increased osteoblastic activity resulting in fibrous replacement of bone and consequent weakening. Parathormone causes increased calcium absorption and increased phosphate excretion by the kidney. The net result in : –

1. T Calcium levels
2. Phosphate levels
3. T Alkaline phosphatase (due to increased osteoblastic activity).

• Clinical features of Primary hyperparathyroidism (Osteitis fibrosa cystica)
• Primary hyperparathyroidism is more common in females and occurs in the third to fifth decades of life. o Clinical features are : ‑

1. Bone pains : This is the most common initial feature. There is tenderness on palpating the bones, especially in the lower limbs and back. Pain is usually associated with general weakness, pallor and hypotonia.
2. Pathological fracture : Fractures occur with trivial injuries and unite in a deformed position. Common sites of fractures are dorso-lumbar spine, neck of the femur and pubic rami.
3. Brown’s tumour : This is an expansile bone lesion, a collection of osteoclasts. It commonly affects the maxilla or mandible, though any bone may be affected.
4. Anorexia, nausea, vomiting and abdominal cramps are common presenting complaints.
5. Occasionally, renal colics with haematuria, because of renal calculus, may occur.

Ans. is ‘c’ i.e., Primary hyperparathyroidism

Radiological features of primary hyperparathyroidism

• X-ray features of primary hyperparathyroidism are : ‑

1. Irregular, diffuse rarefaction of the bones.
2. Salt pepper appearance : The skull bones show a well-marked stippling, but the opaque areas are small pin head size.
3. Loss of lamina dura: A tooth socket is made up of thin cortical bone seen as a white line surrounding the teeth. This is called the lamina dura. It gets absorbed in hyperparathyroidism.
4. Sub-periosteal resorption of the phalanges is a diagnostic feature of hyperparathyroidism (generalized variety). Resorption may also occur at lateral end of the clavicle.
5. Spine shows central collapse of the vertebral body and biconvex discs.
6. Pelvis and other bones show coarse striations with clear cyst-like spaces.
7. Brown ‘s tumour is an expansile lytic lesion, which appears like a bone tumour, generally affecting the maxilla/ mandible.
8. Extra-osseous radiological features such as renal calculi etc. may be present.