ACTA ENDOCRINOLOGICA (BUC)

Objective: Co-existence of Cushing disease and Rathke?s Cleft Cyst (RCC) has been reported in a few cases in the literature so far. We herein describe a rare condition of Cushing disease that might originate from epithelium of RCC. \r\nCase: A 48-year-old woman was admitted to the hospital with complaints of headache, weakness, and weight gain. The patient underwent endoscopic transsphenoidal surgery due to Cushing Disease. Histopathological examination revealed cyst contents and walls compatible with RCC, and normal adenohypophysis and neurohypophysis tissues. Immunhistochemical staining with ACTH, GH, and prolactin were positive on the epithelium of the cyst. \r\nConclusion: In our case Cushing disease might be associated with hormonal activity derived from cyst wall of RCC or disappearance of a small microadenoma during surgical or pathological processing. According to recent data, origin of this lesion and histogenetic link between RCC with Cushing disease could not be explained.

Context. As we progress into the COVID-19 pandemic, it has become apparent that this infection is associated with a multitude of systemic effects, some involving the thyroid gland. The thyroid is also frequently affected in the HCV chronic infection. Objective. The objective of this study is to determine the effects of COVID-19 infection on the presence and severity of thyroid disorders associated with chronic HCV infection, at short and mid-term follow-up. Design. We prospectively evaluated patients with documented HCV- associated thyroid disease (with sustained virologic response after antiviral therapy). Subjects and Methods. The study group consisted of 42 patients with HCV- associated thyroid disease, diagnosed with COVID -19 infection between April and October 2020. We determined serum values of thyroidstimulating hormone, freeT3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies at one and three months after resolution of infection and compared them to the baseline characteristics of the patient. We also evaluated the changes in thyroid substitution treatments or antithyroid drugs. Results. At baseline, out of the 42 patients, 5 presented hypothyroidism under levothyroxine substitution therapy, while 2 presented hyperthyroidism under methimazole therapy; 37 patients had positive antithyroid antibodies. At one month follow-up, we note an increase in serum values of antibodies, with a decrease in TSH, freeT3 and freeT4 levels, correlated with the severity of COVID-19 infection. Two patients required discontinuation of levothyroxine. At 3 months follow-up, lower levels of antithyroid antibodies were recorded, with an increase in TSH levels. No medication doses were adjusted at this time. Conclusion. Among the systemic effects of COVID-19, the impact of thyroid dysfunction should not be underestimated, especially in the presence of pre-existing conditions, such as HCV infection.

Thyroid tumors are the most frequently reported endocrine malignancies. However thyroid collision tumors are rare pathological findings, representing less than 1% of thyroid cancers. In our case, a 50-year-old female patient presented with a complaint of neck swelling. During the exams, nodules were identified in both thyroid lobes. Pathologic analysis of a fine-needle aspiration biopsy(FNA) has been obtained from a 60×50 mm hypoechoic nodule raised suspicion of oncocytic carcinoma(OC). Another FNA was performed on a 17×11 mm hypoechoic solid nodule, revealing features of medullary thyroid carcinoma (MTC). Preoperative whole-body scans indicated no evidence of metastases. The patient subsequently underwent total thyroidectomy and central lymph node dissection. Pathological examination revealed OC, MTC, papillary microcarcinoma (PTMC), simultaneous metastasis of MTC and papillary thyroid carcinoma (PTC) to the same lymph node. The patient's calcitonin level was normalized postoperatively and I-131 ablation therapy was administered to the patient in the ATA high risk category. The patient was monitored under levothyroxine suppression. The simultaneous occurrence of OC, MTC and PTMC of the thyroid gland along with metastases of PTC and MTC in the same lymph node are reported in this case. To the best of our knowledge, this association had not been previously reported in the literature.

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Lingual thyroid is a rare developmental disorder, and it is the result of failure of the thyroid gland to descend from the tongue root to its normal site. The ectopic thyroid with a functioning gland is even rarer. In this case, we present a 44-year-old female patient with a complaint of foreign body sensation, progressive dysphagia and dyspnea due to ectopic thyroid tissue. Her complaints were totally resolved after L-thyroxine treatment. Here we report a patient with functioning ectopic thyroid tissue who had had bilateral subtotal thyroidectomy 10 years ago due to multinodular goiter. In conclusion, if progressive\r\ndysphagia, dyspnea, and foreign body sensation occurs in a patient who had thyroidectomy and living in an endemic goiter region, lingual thyroid may be underlying disorder.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient’s esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient’s parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

Background. A thyroid storm is an extreme disorder that occurs in severe thyrotoxicosis. This condition is life-threatening, with mortality rates up to 10-20%. A typical dose of iodinated contrast media (ICM) contains approximately 13,500 μg of free iodide and 15–60 g of bound iodine, representing an acute iodide load of 90 to several hundred thousand times the recommended daily intake of 150 μg. As a result of sudden exposure to high iodide loads, thyroid hormone regulation can be disrupted, leading to hypothyroidism (Wolff-Chaikoff effect) or hyperthyroidism (Jod-Basedow phenomenon), particularly in those with underlying nodular thyroid disease. Case description. A 37-year-old man presented to the emergency room (ER) with clinical and electrocardiographic signs of acute myocardial infarction. Primary PCI with iodinated contrast was performed. After the intervention, laboratory analyses revealed thyrotoxicosis, and the patient was administered initial thyrosuppressive therapy along with cardiac therapy and discharged from the hospital. One week later, he returned to the hospital with signs of a thyroid storm. Conclusion. This case report aimed to raise awareness regarding the routine evaluation of thyroid function in patients with and without previous signs and symptoms of thyrotoxicosis who had undergone acute myocardial infarction and coronary angiography.

Context. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective. Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods. 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results. P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal Conclusion. The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.