Pathology Associates Of Lexington, P.A.

Parathyroid Pathology

Parathyroid Gland Disease

The most common indication for parathyroid surgery is hyperparathyroidism (enlargement of one or more of the four parathyroid glands, which are usually located around the edges of the thyroid gland...rarely in the mediastinum). Hyperparathyroidism is due to the increased secretion of parathyroid hormone (PTH), which normally circulates in the bloodstream and, at normal levels, stimulates:

absorption of calcium from the intestine.
increased reabsorption of calcium from the kidneys.
resorption of calcium from the bones, mobilizing into blood.

Hyperparathyroid increased hormone secretion results in "renal stones, brittle bones, psychic moans and gastric groans":

an increased calcium level in the blood
gastrointestinal abnormalities "gastric groans"
cognitive impairment "psychic moans"
bone disease "brittle bones"
kidney stones "renal stones"
muscle weakness
other disorders

Hypercalcemia (high-blood calcium level) is often detected on a routine blood chemistry screen. However, a detailed evaluation is required to determine other causes of hypercalcemia besides hyperparathyroidism.

**The Causes of Hypercalcemia:**
hyperparathyroidism: primary vs. secondary
non-parathyroid malignant disease: via parathyroid hormone related peptide via ectopic production of 1,25-dihydroxyvitamin D via lytic bone lesions from metastatic tumors
other non-parathyroid causes: via granulomatous disease (e. g., sarcoid) via thyrotoxicosis via drugs (thiazide diuretics, lithium, vitamin D, etc.) familial hypocalciuric hypercalcemia)

**Parathyroid disease profile:**
disease state:	intact PTH level:	serum calcium level:
parathyroid normalcy	10-65 pg/ml [1.06-6.89pmol/L] [0.106 x pg/ml=pmol/L]	in normal range
normal PTH response	high	low
hypoparathyroid	<21 (low)	low
primary hyperparathyroid	>65 (high)	high
parathyroid cancer	>65 (high)	very high
secondary/tertiary hyperparathyroid	>65 (high)	normal/low
non-parathyrpoid hypercalcemia	<22	high
meds increasing PTH	phosphates, anticonvulsants, steroids isoniazid, lithium, rifampin
meds decreasing PTH	cimetidine, propranolol

Intact PTH can be broken down into several molecular fragments: N-terminal, C-terminal, midregion, and PTH (7-84). There is a PTH bio-intact (1-84) test. And there is a PTH-related protein.

If primary hyperparathyroidism (disease originating in the parathyroids themselves) is the cause of hypercalcemia, surgery is the treatment of choice. Eighty-five percent of patients with primary hyperparathyroidism have a single parathyroid gland adenoma (or, very rarely, carcinoma) and are cured with the removal of the single enlarged gland. Nearly 15 percent of patients with primary hyperparathyroidism have multi-gland hyperplastic disease and will require either removal of approximately 3½ parathyroid glands, or total parathyroidectomy with immediate parathyroid autotransplantation (that half minced & re-implanted between muscle fibers in the sternal aspect of well vascularized sternocleidomastoid muscle, marked by metal clips...L07-10526). Sestamibi nuclear medicine scan can often localize the adenoma pre-operatively (we have this at LMC). In October 2006, we began offering intra-operative PTH determinations to assure that the reason (s) for elevation of PTH had been removed.

Surgery is also required for select patients with secondary hyperparathyroidism (increased PTH & low/normal calcium) and for tertiary hyperparathyroidism (increased PTH & increased calcium). These patients develop parathyroid gland enlargement as a consequence of other metabolic disorders, most commonly renal failure. This excess hormone mobilizes great amounts of calcium and phosphorous. Surgery of choice is total parathyroidectomy with immediate partial parathyroid autotransplantation [LMC-02-3095] into a location which is easily accessible in case the glandular transplant becomes too active (see above). The immediate postoperative course requires pretty intense monitoring to prevent problems with the proper serum level of calcium.

**Parathyroid & intra-operative decisions:**
parathyroid hyperplasia: decreased gland fat; may be nodular; may see a mitosis. primary: increased serum calcium and PTH & hypophosphatemia. secondary: increased serum calcium and PTH & hyperphosphatemia.
parathyroid adenoma: rare to affect more than one gland or be more than one nodule; & the adenoma has decreased fat. May see a mitosis. look for remnant of normal gland. "atypical adenoma": when worrisome but can't meet criteria of carcinoma...especially if no demonstrable vascular or soft tissue invasion ².
parathyroid carcinoma: think malignant if see mitosis in frozen section high percentage of cases have very high serum calcium and very high percentage of cancer cases in patients with renal disease². (1) contain thick acellular fibrous bands, (2) high mitotic rate, & (3) capsular or vascular invasion...these are the 3 most useful criteria of cancer². S-phase fraction >4%².

References:

Keffer JH, et. al., The Handbook of Clinical Pathology, 2nd Ed., 2000. (EBS's office)
Haber MH, et. al., Differential Diagnosis in Surgical Pathology, 2002. (EBS's office)

(posted 18 May 2002; latest addition 24 November 2007)