Atypical parathyroid adenomas as a rare cause of primary hyperparathyroidism - in an academic institution experience

BACKGROUND Primary hyperparathyroidism (PHPT) is caused by benign and malignant conditions. Most commonly by typical adenoma/single gland disease (PA) - this is 80-85% cases of PHPT. Parathyroid hyperplasia or multiple gland disease accounts for 10-15% of cases of PHPT. Atypical parathyroid adenoma (APA) and carcinoma (PC) - very rare conditions - are both responsible for PHPT in approximately 0,5 - 1,5% of cases. OBJECTIVES To estimate occurrence of atypical parathyroid adenoma, parathyroid carcinoma and parathyroid hyperplasia along with characterize them based on their etiology, clinical presentation, diagnosis and treatment METHODS We performed a retrospective study and enrolled 1,019 patients with primary hyperparathyroidism undergoing parathyroidectomy at academic Department of General and Endocrine Surgery between 1983 and 2018. RESULTS Out of 1,019 cases of primary hyperparathyroidism, 850 (83.4%) cases were due to typical parathyroid adenoma (PA), 135 (13.2%) cases were due to parathyroid hyperplasia, 29 (2.8%) cases were due to parathyroid carcinoma (PC), and 5 (0.5%) cases were due to atypical parathyroid adenoma (APA).

Metastatic Thyroid Cancer After Thyroidectomy in Patient With Neuroendocrinal Tumor

Background: Multiple endocrine neoplasia type 2 is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. Classical multiple endocrine neoplasia 2A is the most common variant. It is a heritable predisposition to medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. The respective frequency of these tumors in classical MEN2A is over 90 percent for MTC, approximately 10 to 50 percent for pheochromocytoma, and 10 to 20 percent for multigland parathyroid hyperplasia. Discussion: our interesting patient is a 67-year-old patient with past medical history of prophylactic total thyroidectomy at the age of 25 years after a positive pentagastrin test (sister was diagnosed with MTC, pheochromocytoma),niece with metastatic kidney cancer.at that time, patient had benign pathology. Patient presented to the ED with a complain of shortness of breath after being referred by her PCP for evaluation of possible pneumonia. In the ED, her vitals were within normal, chest X-ray was done and didn’t show pneumonia but the patient was found to have elevated procalcitonin of 22.7 ng/mL(0.09 ng/mL) CT chest was done and showed enlarged necrotic cervical lymphadenopathy which was confirmed by obtaining CT of the neck. Patient had right cervical LN core biopsy, pathology was positive for medullary thyroid cancer with Immunohistochemical studies positive for TTF-1, chromogranin, synaptophysin and calcitonin, testing for pheochromocytoma came back within normal, CEA 70.7ng/ml (<0.25 ng/ml), calcitonin 2949 pg/ml (5 pg/mL) Chromogranin was high at 453 ng/ml (25 - 140 ng/mL) had PET CT with multiple low right cervical and supraclavicular lymph nodes with internal calcifications and abnormal FDG activity, which were suspicious for medullary thyroid cancer metastases, she eventually had radical neck dissection with pathology from inferior parathyroid gland positive for medullary thyroid cancer and 12/15 regional LN positive for malignancy, after the procedure her calcitonin dropped nicely to 194pg/ml, CEA dropped to 4.0, chromogrannin to 394, she was referred to genetic testing and tested positive for pathogenic variant within RET (c.1859G>T, p.Cys620Phe), which is known to be associated with multiple endocrine neoplasia type 2A, she is currently being evaluated for Lutathera treatment. Conclusion: In contrast to MEN1, in which the long-term benefit of early diagnosis by genetic screening is not well established, early diagnosis by screening of “at-risk” family members in MEN2 with positive RET mutation kindreds is essential because MTC is a life-threatening disease that can be cured or prevented by early thyroidectomy. Total thyroidectomy has been recommended for patients as young as 3 years for MEN2A if they contain the genetic mutation.

Acromegaly and non‐parathyroid hormone‐dependent hypercalcemia: a case report and literature review

Background Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare. Case presentation Here we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range. Conclusions Mild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS

Objective: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in survivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with their connections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dysmetabolic relationships. Materials and methods. Clinical effects of ionizing radiation on the endocrine system in persons affected by the Chornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample (n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. The generally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental (ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statistical methods were applied. Parametric and nonparametric statistical methods were used in data processing. The value of p < 0.05 was considered a statistically significant. Results. No significant difference was found in the incidence of carbohydrate metabolic disorders in the Chornobyl NPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, residents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia was detected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathyroid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels were significantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects. The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine» period with diagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml, p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/deficiency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteopenia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screening for parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children born to parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D (11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT). A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D (r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irradiated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thyroid function, impaired carbohydrate and fat metabolism and the state of parathyroids. Conclusions. No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW, evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathyroid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size. There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathyroid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strong association between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of parathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine» period with diagnosed parathyroid hyperplasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group. Key words: ChNPP accident, irradiation, accident survivors, accident consequences clean-up workers, ionizing radiation, parathyroids, hyperplasia, hyperparathyroidism, thyroid.

Tumour Induced Osteomalacia: Rapid Clinical and Biochemical Control Using Octreotide

Aims: To assess the effects of short acting octreotide on the Fibroblast Growth Factor-23 levels and the clinical outcome in a bedridden patient with Tumour Induced Osteomalacia. Presentation of the Case: A 40-year old female, presented with a 16-year history of progressive weakness and bone pains. Severe hypophosphatemia had been documented throughout and she had been treated intermittently with oral phosphate and various preparation of vitamin D. Hypercalcaemia due to parathyroid hyperplasia was diagnosed 4 years previously. In the last 2 years she had undergone bilateral hip prostheses and removal of 2 hyperplastic parathyroid glands. When seen by us she was bedbound with severe restriction of all joint movements, there was a palpable left buttock mass 4x4 cm. Tumour induced osteomalacia was suspected and confirmed by finding grossly elevated levels of Fibroblast growth factor (FGF-23) 3400 Ru/ml (44-140).The serum calcium 2.5 mmol/L (n 2.1-2.5), phosphate 0.3 mmol/L (n 0.8-1.45).Alkaline phosphatase (ALP) 400 U/L ( n 35-104), Parathyroid hormone (PTH) 27 pmol/L (n 1.6-9.3) , and creatinine 70 umol/L (n 45-84). Octreotide scanning revealed focal uptake in the buttock corresponding to the MRI findings. Treatment with octreotide 100 mcg 8 hourly was given for 10 days before surgery. By day 3 the FGF-23 had fallen to 400 and on the day of surgery was 210 Ru/ml. A benign mesenchymal tumour was completely resected and 8 weeks following surgery the FGF-23 was normal, serum calcium 2.7 mmol/L, serum phosphorus 0.63 mmol/L, ALP 690 U/L, PTH 22 pmol/L . The patient was then able to walk in a Zimmer frame after 2 months. Since then she recovered completely, she is able to walk without assistance for the last 2 years. Conclusion: This case provides an example of successful use of short acting octreotide in controlling the disease and demonstrated a rapid normalisation of elevated FGF-23 levels achieved during treatment with octreotide. It describes a rare association between tumour induced osteomalacia (TIO) and parathyroid hyperplasia, the value of octreotide scanning in tumour localisation and the potential for using LA octreotide therapy in patients with responsive tumours that cannot be localised or removed for any reason.

Recurrent Acute Pancreatitis in Pregnancy Caused by Parathyroid Hyperplasia: A Case Report and Literature Review

Background: Hypercalcemia during pregnancy leads to multiple maternal and fetal complications. To date, fewer than 30 cases of primary hyperparathyroidism (PHPT)-induced pancreatitis have been diagnosed during pregnancy. Most cases have been caused by a parathyroid adenoma. In the present report, the author described the first case of PHPT due to parathyroid hyperplasia presented with recurrent, acute pancreatitis during pregnancy. Case Report: A 38-year-old female, with a history of acute pancreatitis during her first pregnancy, presented with severe epigastric pain, nausea, and vomiting for three days at 24 weeks of gestation. Parathyroid-dependent, hypercalcemia-induced recurrence of pancreatitis was diagnosed based on the clinical presentation and laboratory investigations. An ultrasound on her neck revealed a possible parathyroid adenoma located on the inferior pole of the left thyroid gland. She underwent an uneventful left-lower parathyroidectomy. The pathological examination revealed parathyroid hyperplasia. Her serum calcium and parathyroid hormone levels returned to normal after surgery. She delivered a healthy male newborn at gestational age 38 weeks without any complications. Conclusion: PHPT-induced acute pancreatitis during pregnancy is rare. Hypercalcemia, involving both total and ionized calcium, should be investigated in pregnant women who present with acute pancreatitis. Early diagnosis and appropriate management can significantly improve the maternal, fetal, and pregnancy outcomes. Keywords: Hypercalcemia, Recurrent pancreatitis, Pregnancy, Primary hyperparathyroidism, Parathyroid hyperplasia