Parathyroid Gland Disorders

Primary hyperparathyroidism is characterized by excessive secretion of parathyroid hormone (PTH) and most commonly occurs in older women. The most common etiological factor is a parathyroid adenoma, comprising focal clusters of chief cells. Familial cases often stem from MEN1 or MEN2A syndromes, with the former typically involving a parathyroid adenoma (MEN1) and latter due to parathyroid hyperplasia (MEN2).

Histologically, these adenomas present as well-encapsulated masses of purple chief cells, often inducing atrophy in the remaining 3 parathyroid glands (parathyroid hyperplasia causes enlargement of all 4 glands). Elevated PTH levels disrupt calcium and phosphate homeostasis, leading to hypercalcemia and hypophosphatemia. PTH increases the synthesis of calcitriol, further augmenting calcium levels, and also has an activating effect on osteoclasts, leading to bone resorption. Skeletal manifestations include conditions like osteitis fibrosa cystica, featuring brown tumors of osteoclasts mixed with fibrous tissue and poorly mineralized bone. Other bone abnormalities include subperiosteal thinning of the phalanges, clavicles, & skull (‘salt & pepper’ appearance) as well as increased alkaline phosphatase low bone mineral density. Renal effects include type II renal tubular acidosis due to impairment in bicarbonate reabsorption in the proximal tubule.

Hypercalcemia is a hallmark feature primary hyperparathyroidism and leads to a variety of clinical consequences, often remembered using ‘stones, bones, abdominal moans, and psychiatric overtones.’ Renal complications include calcium stones due to hypercalciuria, as well as polyuria and polydipsia from defects in the renal capacity to concentrate urine. Severe, chronic hypercalcemia can escalate into metastatic calcification in the renal tubules, leading to end-stage renal disease, as well as calcifications in the lungs, brain, and skin.

Gastrointestinal effects include constipation from altered smooth muscle tone and autonomic function, and peptic ulcer disease from excessive gastrin release. Pancreatic involvement can lead to pancreatitis, either due to calcium deposition or trypsinogen activation. Neuropsychiatric symptoms such as confusion, anxiety, psychosis, & seizures can also occur.

Diagnosis typically employs a Technetium-99m-sestamibi radionuclide scan to localize hyperfunctioning parathyroid tissue prior to surgical intervention. The primary treatment for symptomatic hypercalcemia is surgery, which may result in a phenomenon known as hungry bone syndrome. This involves a rapid increase in bone mineralization due to an abrupt decrease in PTH, leading to a sudden rise in osteoblast activity. This can consequently cause rapid decreases in circulating levels of calcium, phosphate, and magnesium.

Secondary hyperparathyroidism commonly arises in the context of chronic kidney disease (CKD). CKD impairs the synthesis of calcitriol due to a deficiency of 1-alpha-hydroxylase, leading to low calcitriol and hypocalcemia. The low calcium, coupled with hyperphosphatemia from impaired renal phosphate excretion, stimulates excessive PTH secretion, resulting in diffuse parathyroid hyperplasia. The clinical effects involve bone abnormalities like osteitis fibrosa cystica and increased alkaline phosphatase levels.

Tertiary hyperparathyroidism occurs as a long-term consequence of secondary hyperparathyroidism, and is characterized by nodular parathyroid hyperplasia and autonomously functioning parathyroid glands that result in hypercalcemia and hyperphosphatemia, as well as low calcitriol from persistent CKD. Severe hypercalcemia in these cases can result in metastatic calcification in the lungs, brain, and skin. Treatment of choice for tertiary hyperparathyroidism is parathyroidectomy.

Hypoparathyroidism is often caused by surgical injury to the parathyroid glands but can also occur in conditions like DiGeorge syndrome or type 1 autoimmune polyglandular syndrome. Hypoparathyroidism leads to hypocalcemia and hyperphosphatemia due to PTH deficiency, manifesting clinically with a spectrum of symptoms. These can range from mild issues such as perioral numbness & paresthesias to severe complications like tetany, seizures, & heart failure. Specific clinical signs of hypocalcemia include Chvostek's sign and Trousseau's sign.