pth Flashcards
Parathyroid Glands
Chief cells – basic cell type, contain granules of PTH
Express calcium sensing receptor
Recall G-Protein Calcium Sensor for PTH release
Synthesize and secrete PTH in response to low calcium
Oxyphil cells – appear at puberty, present as single cells of small clusters
Have many mitochondria; secretory granules are absent
activity of the PT glands is controlled by the
evel of free (ionized) calcium in the bloodstream
Decreased levels of free calcium stimulate the synthesis and secretion of PTH
An increased level of free calcium, in turn, inhibits PTH secretion
Hypercalcemia
Serum PTH levels are inappropriately elevated for serum calcium levels
Clinically apparent hypercalcemia
Malignancies
Solid cancers secrete PTH related protein (PTHrp)
Solid tumors (lung, breast, head and neck and renal cancers) and hematologic malignancies mostly multiple myeloma
Primary hyperparathyroidism
Autonomous, spontaneous overproduction of PTH by PT tissue
Cyclin D1 and MEN1 mutations
5-10% are familial-associated with MEN 1 and MEN 2A syndromes
PT Hyperplasia
Sporadic/component of MEN syndrome
All 4 glands or asymmetric involvement with sparing of 1 or 2 glands
Parathyroid carcinomas
May involve 1 gland, gray-white irregular masses that exceed 10g, cytological similarity to adenomas
Invasion of surrounding tissues and metastasis are only reliable criteria for malignancy
Morphologic changes in other organs
Increased osteoclastic activity results in increased bone resorption
Increased osteoblastic activity results in formation of new bony trabeculae
Resultant bone comprises of widely spaced thin trabeculae and in severe cases, marrow with hemorrhage, cyst formation and fibrosis
Occasionally form masses composed of giant cells and hemorrhagic debris
Urinary tract – urinary tract stones, nephrocalcinosis (calcification of renal interstitium and tubules)
Secondary hyperparathyroidism
Due to conditions causing chronic DECREASED calcium which lead to compensatory PT hyperplasia
Chronic renal failure is most common cause – decreases phosphate excretion leading to elevated serum phosphate levels that directly depress serum calcium levels
Loss of renal substance reduces availability of alpha-1-hydroxylase
Tertiary hyperparathyroidism
When PT activity becomes autonomous and excessive with resultant hypercalcemia
Treatment – parathyroidectomy
Hypoparathyroidism
ongenital absence, surgery/radiation, autoimmune, familial
Clinical manifestations – related to severity and chronicity of hypocalcemia
Tetany, neuromuscular irritability
Anxiety and depression, confusional states, hallucinations, and frank psychosis
Calcifications of basal ganglia, Parkinsonian-like movement disorders, and increased intracranial pressure with resultant papilledema
Characteristic prolongation of QT interval in ECG
Pseudohypoparathyroidism
Hypoparathyroidism occurs because of end-organ resistance to actions of PTH
Serum PTH levels are normal or elevated
C cells of thyroid
Secrete the hormone calcitonin
Lowers serum calcium
Goitrogens
Chemical agents that inhibit function of thyroid gland
Suppress T3/T4 synthesis
Hyperthyroidism
Hypermetabolic state caused by elevated circulating levels of free T3 and T4
Primary
Diffuse hyperplasia (Graves disease) – 85% of cases
Toxic multinodular goiter, toxic adenoma, iodine-induced hyperthyroidism, neonatal thyrotoxicosis
Secondary – TSH-secreting pituitary adenoma
Thyroid storm
Abrupt onset of severe hyperthyroidism; results from an acute elevation in catecholamine levels,
Apathetic hyperthyroidism
Thyrotoxicosis occurring in elderly where typical features are blunted
Diagnosis is often made during lab work-up for unexplained weight loss or worsening CV disease
dx via Lab findings – low TSH (most useful), elevated free T4/free T3, radioactive iodine uptake test
Graves disease
Most common cause of endogenous hyperthyroidism is characterized by a triad of clinical findings
Hyperthyroidism – diffuse, hyperfunctional enlargement of thyroid
Infiltrative ophthalmopathy with resultant exophthalmos
Localized, infiltrative dermopathy
Thyroid-stimulating immunoglobulin – IgG antibody binds to TSH receptor and mimics the action of TSH
Increased risk for other autoimmune diseases, such as SLE, DM1, etc
Lab findings – elevated free T4/T3 levels, depressed TSH levels,
Hypothyroidism
Structural or functional derangement that interferes with production of adequate levels of thyroid hormone
Fairly common disorder – population prevalence of overt hypothyroidism is 0.3%, while subclinical hypothyroidism can be found in >4%
Nearly 10x more common in women than men
Can result from a defect anywhere in hypothalamic-pituitary-thyroid axis
Primary (more common)
Congenital
Acquired – surgical or radiation-induced ablation, drugs
Autoimmune – most common cause in iodine-sufficient areas (Hashimoto)
Lab findings – elevated TSH, low T4
Secondary hypothy
Pituitary failure/hypothalamic failure
Lab findings – low TSH, low T4
Classical clinical manifestations
Cretinism – develops in infancy or early childhood, clinically characterized by short stature, severe Mental Retardation (MR) and coarse facial features
Myxedema – older child or adult, patients are listless, cold-intolerant,
cause:Thyroiditis – inflammation of thyroid gland, cause of primary hypothyroidism
Hashimoto thyroiditis
Most common cause of hypothyroidism in areas where iodine levels are sufficient
Characterized by gradual thyroid failure because of autoimmune destruction of thyroid gland
Most prevalent between 45-65 years of age
Female predominance
Morphology – diffusely enlarged with intact capsule
Riedel thyroiditis
extensive fibrosis involving thyroid and contiguous neck structures
Clinically stimulates a thyroid carcinoma
Subacute lymphocytic (painless) thyroiditis
Middle-aged women, characterized by mild painless symmetric thyroid enlargement
Postpartum thyroiditis – occurs in postpartum period in up to 5% of women, circulating anti-thyroid peroxidase Abs
Goiter
Enlargement of thyroid, most common manifestation of thyroid disease
Degree of thyroid enlargement is proportional to level and duration of thyroid hormone deficiency
Pathogenesis – impaired synthesis of thyroid hormone, compensatory rise in serum TSH level, hypertrophy/hyperplasia of thyroid follicular cells to ensue a euthyroid metabolic state
In case compensatory responses are inadequate, the result is goitrous hypothyroidism
Diffuse non-toxic (simple) goiter
colloid goiter
Endemic goiter – in areas where soil, water, and food supply contain low levels of iodine
Particularly dietary substances – goitrogens
Sporadic goiter – less frequent
