Pathology Notes

Tertiary hyperparathyroidism   Updated: 07/02/2023 © Jun Wang, MD, PhD General features Autonomous hypersecretion of PTH due to parathyroid hyperplasia/adenoma arising from longstanding secondary hyperparathyroidism Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation Often detected after hemodialysis or transplantation corrects the renal disease Clinical presentations History of secondary hyperparathyroidism Presentation of underlying disorders Possible diffuse calcinosis Key laboratory findings Abnormalities of underlying disorder, such as abnormal renal function test Elevated levels of PTH High serum phosphorus Elevated calcium Treatment Surgery Back to parathyroid pathology Back to pathology of endocrine system Back to contents

Secondary hyperparathyroidism   Updated: 02/08/2024 © Jun Wang, MD, PhD General features Overproduction of parathyroid hormone Secondary to a chronic abnormal stimulus, such as chronic hypocalcemia Bone changes similar by less severe than primary hyperparathyroidism Risk factors Renal failure (phosphorus retention causes hypocalcemia) Inadequate calcium intake Steatorrhea (failure to absorb Vitamin D) Vitamin D deficiency or resistance Clinical presentations Presentation of underlying disorders Multiple glands hyperplasia Key pathogenesis Chronic low calcium level due to conditions, such as renal failure Chronic phosphate retention causes excess FGF23 secretion FGF23 reduces renal 1,25(OH) 2 D production Low calcium and high phosphate stimulate PTH secretion and parathyroid proliferation Here is a video explaining this clearly. Key laboratory findings Abnormalities of underlying disorder, such as abnormal renal function test Elevated levels of PT

Pseudohypoparathyroidism   Updated: 01/25/2021 © Jun Wang, MD, PhD General features Heterogeneous group of disorders  More common in female Onset usually starts at childhood Insensitivity to the biologic activity of PTH Type 1: Commonly defects in GNAS1, heterozygous Type 2: No skeletal or developmental defects, normal urinary cAMP response Clinical presentations Associated with hypocalcemia Hypocalcemia, hyperphosphatemia, increased PTH Type 1 1a: Albright hereditary osteodystrophy , autosomal dominant , , characteristic appearance (short stature, obesity, round facies, shortened metacarpals and metatarsals), deficiency of Gs alpha protein , defected functions of TSH, antidiuretic hormone, gonadotropins and growth hormone Pseudopseudohypoparathyroidism : Insufficient Gs alpha protein function , appearance of Albright hereditary osteodystrophy without PTH resistance 1b: Resistance to PTH only in the kidneys, genetic basis unknown 1c: Clinical and laborator

Primary hyperparathyroidism   Updated: 02/05/2024 © Jun Wang, MD, PhD Definition Autonomous overproduction of parathyroid hormone General features More common in women; usually age 50+ NO evidence of prior parathyroid stimulation by renal or intestinal disease Most common cause: Adenoma Other causes: parathyroid hyperplasia and carcinoma Key pathogenesis Autonomous overproduction of parathyroid hormone Subsequent activation of osteoclast Clinical presentations May be asymptomatic Incidental finding of hypercalcemia Associated with hypercalcemia and excessive calcium resorption Bones : Osteoporosis, osteitis fibrosa cystica (brown tumor) Stones : Renal calcium stones, nephrocalcinosis Abdominal groans : Nausea, peptic ulcers (associated with high serum gastrin caused by hypercalcemia), constipation, pancreatitis, gallstones Psychic moans : Depression, lethargy, seizures Others: Proximal myopathy, Weakness, fatigue, calcifications Key laboratory findin

Primary chief cell hyperplasia   Updated: 07/02/2023 © Jun Wang, MD, PhD General features Most common type of primary parathyroid hyperplasia Associated with MEN 1, 2A/2, but NOT MEN 2B/3 May be pseudoadenomatous (one gland enlarged) or occult (all glands normal size but histologically hyperplastic) Clinical presentations Hyperparathyroidism Pathological features Usually involving all glands Evenly enlarged parathyroid glands Increase quantity of chief cells, usually diffusely Usually NO rim of normal tissue identified under microscope May have clear cell changes (water clear cell hyperplasia) Laboratory findings High PTH Hypercalcemia Treatment Surgery Back to parathyroid pathology Back to pathology of endocrine system Back to contents

Parathyroid carcinoma   Updated: 07/02/2023 © Jun Wang, MD, PhD General features Rare, usually functioning Recurrence and metastasis common Diagnosis based on invasion and metastasis, NOT cytological features Clinical presentations Usually detected because of palpable neck mass May cause primary hyperparathyroidism Vocal cord paralysis if local nerves involved Pathological features Large irregular mass Evidence of invasion /metastasis Laboratory findings High PTH Hypercalcemia Treatment Surgery Radiation Back to parathyroid pathology Back to pathology of endocrine system Back to contents

Parathyroid adenoma   Updated: 07/02/2023 © Jun Wang, MD, PhD General features Most common cause of primary hyperparathyroidism More common in women, usually in 30’s Usually solitary lesion, monoclonal, functionally active Difficult to diagnose - best criterion is lack of hypercalcemia for 5 years after excision Clinical presentations Associated with hypercalcemia and excessive calcium resorption Key radiologic features Sestamibi scan Useful in detecting adenomas in patients with primary hyperparathyroidism High specificity, low sensitivity Not positive for hyperplasia Not for secondary hyperparathyroidism Pathological features Usually solitary enlarge parathyroid gland Nodular growth with rim of compressed normal parathyroid tissue Most commonly composed of chief cells, with mixture of oncocytes Non-neoplastic glands usually normal in size or shrunken due to feedback inhibition from elevated serum calcium Genetic abnormalities MEN1 gene mut