HYPERPARATHYROIDISM mild and sometimes only intermittent hypercalcemia . The mean s ca is < 1.0 mg/dL above nl nonspecific symptoms: fatigue, weakness, anorexia, mild depression
CLASSICAL MANIFESTATIONS Anorexia, nausea, constipation, Polydipsia, and polyuria. Osteitis fibrosa cystica: is rare (<5 % of pts) Nephrolithiasis: most common (15-20 %) of
newly diagnosed pts . Osteitis fibrosa cystica bone pain X-ray
Subperiosteal bone resorption Tapering of distal clavicles
Before after surgery
Brown tumors of pelvis ( ? PTH ca) Neuromuscular/Psych symptoms Neuromuscular: weakness and fatigue. Myopath is rare
Neuropsychiatric: depressed mood, psychosis, Bone mineral density Decreased BMD : cortical sites (forearm and hip) > cancellous sites (spine)
Cardiovascular HTN is common Mean carotid intima-media thickness was significantly higher compared with controls Mortality
increased mortality: primarily due to CVS disease DIAGNOSIS Serum calcium : confirmed PTH
Measurement of PTH -80-90 %: high PTH -10-20 %: minimally elevated or high normal DIFFERENTIAL DIAGNOSIS
1. Malignancy: often evident clinically Intact PTH: very low in hypercalcemia of malignancy mediated by PTHrP 2. FHH: an inactivating mutation in the Ca-SR in the parathyroid glands and the kidneys
- A f/h of hypercalcemia (young children) - absence of symptoms and signs of hypercalcemia 15- 20 % of pts with FHH: mildly elevated PTH FHH vs primary hyperparathyroidism:
low urine ca excretion and Ca/Cr clearance ratio 3. Drugs: a- thiazide diuretics and lithium. reduce urin Ca excretion and can cause mild
hypercalcemia (up to 11.5 mg/dL ) thiazide should be stopped and calcium and PTH assessed 2-3 months later B- Lithium bipolar disorder
S/E: nephrogenic DI, hypothyroidism and hyperparathyroidism. PTH less inhibited by calcium It decreases renal Ca excretion (independent of PTH)
4. Secondary hyperparathyroidism: High PTH Calcium: NL or low - renal failure - inadequate calcium intake or absorption: - vitamin D deficiency
- malabsorption . TESTS TO CONFIRM PRIMARY HYPERPARATHYROIDISM 1. Urinary Ca excretion : distinguishes PHPT from FHH
If low ( < 200 mg/day): FHH vs hyperparathyroidism with vit D deficiency 2. 25 Vitamin D: replete low levels ( 50 nmol/L) before management decisions
3. Serum phosphorus: decreased or low nl Renal imaging: renal U/S should be performed if kidney stones are suspected . Localization studies: U/S,
technetium-99m sestamibi CT, or MRI intraoperative PTH monitoring Management of primary hyperparathyroidism
- Parathyroidectomy: first line therapy - indicated in asymptomatic patients if : S Ca >= 1.0 mg/dL above the upper nl Cr clearance <60 mL/min BMD at hip, LS, or distal radius (T score <-2.5) and/or previous fragility fracture
Age < 50 years ALTERNATIVES TO SURGERY Avoid: thiazide lithium volume depletion
prolonged bed rest / inactivity high calcium diet (>1000 mg/day) Encourage physical activity Adequate hydration to minimize the risk of nephrolithiasis.
Ca intake (800-1000 mg/day). A low calcium diet may lead to further increases in PTH secretion and bone disease Maintain vitamin D intake (400-600 IU/ d) Monitoring: S Ca and Cr annually and bone
density (hip, spine, and forearm) every 1-2 years is sufficient. Drug therapy Bisphosphonates: pts who do not meet surgical criteria or who
prefer to avoid surgery Calcimimetics: activate the Ca-sensing R in the parathyroid gland, and inhibit PTH secretion - cinacalcet: - 2 hyperparathyroidism in renal failure
- hypercalcemia in parathyroid cancer HYPERCALCEMIA TREATMENT OF HYPERCALCEMIA regardless of etiology
INDICATIONS FOR TREATMENT 1. Asymptomatic hypercalcemia (Ca <12 mg/dL) do not require immediate treatment. 2. S Ca of 12-14 mg/dL: acutely requires more aggressive measures 3. S Ca >14 mg/dL requires treatment,
regardless of symptoms. SALINE HYDRATION isotonic saline at 200-300 mL/h initially if edema: loop diuretic may be used
CALCITONIN Salmon calcitonin (4 IU/kg) IM or sc q 12 hrs. Nasal calcitonin is not effective lowers ca by 1-2 mg/dL within 4-6 hrs Efficacy limited to the first 48 hrs, even with repeated doses (tachyphylaxis)
B. HYPOCALCEMIA WITH HIGH PTH 1. PTH resistanc: (Pseudohypoparathyroidism): - childhood - low Ca, high phosphate, and elevated PTH 2. Vitamin D deficiency or resistance
3. Extravascular deposition: deposition in tissues or binding within the vascular space 4. Hyperphosphatemia : CKD / ARF/ rhabdomyolysis/ tumor lysis 5. Osteoblastic metastases: breast or prostate
cancer 6. Acute pancreatitis :precipitation of calcium soaps in the abdominal cavity 7. Sepsis or severe illness: hypocalcemia in critically ill or postsurgical pts 80-90 %.
C. DISORDERS OF MG METABOLISM: 1. mg depletion: PTH resistance (Mg < 1 mg/dL) or by decreasing PTH secretion - Malabsorption - Chronic alcoholism - Cisplatin therapy
- diuretic therapy - aminoglycosides 2. Severe hypermagnesemia: suppressing the secretion of PTH ( mg > 6 mg/dL) Treatment of hypocalcemia IV calcium :
- acute symptomatic pts - asymptomatic hypocalcemia with acute decreases to 7.5 mg/dL 1 - 2 g of calcium gluconate ( 90 - 180 mg elemental calcium) in 50 mL of 5 % D over 10 - 20 minutes iv solution: 100 mL (10 amp) of 10 % calcium
gluconate in 1000 mL of 5 % dextrose in water, at 50 mL/h Iv calcium continued until the patient is recieving oral calcium and Calcitriol Oral calcium: mild acute hypocalcemia (7.5 8.0 mg/dL) or for chronic hypocalcemia.
1500 - 2000 mg of elemental calcium Vitamin D supplement is also needed. Thank you Clinical manifestations and diagnosis of MEN 1
- pancreatic islet cells Also: - duodenum: gastrinomas, and carcinoid tumors - adrenal adenomas, and lipomas DEFINITION OF MEN1
presence of two of the three main MEN1 tumor types (parathyroid, entero-pancreatic endocrine adenomas, and pituitary adenomas) Familial MEN1 : index MEN1 case with at least 1 relative with 1 of 3 main MEN1 tumors
PRIMARY HYPERPARATHYROIDISM in MEN 1 most common : almost 100 % by age 40-50 yrs 1-2 % of primary hyperparathyroidism are due to MEN1 different features from the sporadic form :
The M: F ratio is even in MEN1 in contrast to the female predominance in sporadic form in MEN1 presents in the 2nd - 4th decade of life (2 decades earlier than in sporadic form) Multiple gland involvement in MEN1. 80-85 % of pts with sporadic disease have
single parathyroid adenomas. A high rate of recurrent hyperparathyroidism after subtotal parathyroidectomy. recurrence rate > 50 % at 12 yrs .
Diagnosis hypercalcemia with inappropriately high PTH PITUITARY ADENOMAS
Clinically apparent in 15 - 20 % by CT or MRI ; Pathological prevalence > 60 % . The most common type is a prolactinoma,
GH-producing, ACTH-producing, gonadotroph and clinically non-functioning tumors can also occur . Multiple tumors are rare macroadenomas
- 85 % had macroadenomas versus 42 % in non-MEN1 patients - MEN1 patients had tumors that were larger and more aggressive than those in non-MEN patients
The approach to diagnosis and therapy of pituitary adenomas in patients with MEN1 is similar to that in patients with sporadic adenomas. PANCREATIC ISLET CELL/GASTROINTESTINAL
ADENOMAS 1/3 of pts with MEN1 The most common cause of symptomatic disease is the Zollinger-Ellison (gastrinoma) syndrome, leading to multiple peptic ulcers. 60 % of pts with MEN1 have ZES or
asymptomatic elevation in serum gastrin MEN1 is present in 20- 60 % of pts with ZES Symptomatic insulinomas also occur VIPomas and glucagonomas are rare The prevalence of nonfunctioning tumors is
30- 80 %. clinically nonfunctioning Pancreatic Endocrine Tumors may be malignant causing liver metastases Zollinger-Ellison syndrome
the gastrinomas in MEN1 are multifocal, often very small the duodenum is a common site of gastrinomas in MEN1 and sporadic form Tumors in the pancreas do not usually secrete gastrin
The risk of death from malignant MEN1 gastrinoma is < sporadic ZES : initial manifestation of MEN1 in 40 % The onset of ZES symptoms preceded the dx
of hyperparathyroidism in 45 % of pts Pituitary disease occurred in 60 % of patients. Diagnosis Suspected clinically by the presence of
multiple peptic ulcers or symptoms like diarrhea similar to sporadic form nonfamilial gastrinoma: the usual cause is ectopic ACTH release from the islet-cell tumor.
Patients with MEN1 and ZES who develop Cushing's syndrome usually have a corticotroph adenoma of the pituitary Insulinoma
In MEN1 are often small, may be multiple, Nonfunctioning pancreatic Endocrine tumors Detected as early as ages 12 -14 in asymptomatic children
The risks of metastasis and death are low for tumors 20 mm Carcinoid tumors Thymic carcinoid tumors occur in MEN1 (2.6 -5 %), - mostly in men
- heavy smoking ? a risk factor Thymic carcinoids : are typically nonfunctional (in contrast to the substantial incidence of ectopic Cushing's syndrome in pts with sporadic thymic carcinoid), and tend to be aggressive
Thymic carcinoids in MEN1 CT and MRI were sensitive for detecting the tumors All patients underwent surgical resection with high rate of recurrence
Cutaneous tumors Angiofibromas and collagenomas were more common in MEN1 patients lipomas were present in 17 % others
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