ACTA ENDOCRINOLOGICA (BUC)

Context. 49,XXXXY syndrome is an aneuploidy that affects males and is commonly referred to as a variant of Klinefelter Syndrome. It presents a frequency of 1:85,000 to 100,000 births and an etiology related to non-disjunction of homologous chromosomes. Findings include skeletal abnormalities, hypogonadism, and cognitive impairment. Turner syndrome is also an aneuploidy of the sex chromosomes, which affects women, and has a prevalence of 1:2000 to 2500 births and a phenotype characterized by short stature and sexual infantilism. Objective. The objective of this article was to study the literature, investigate the family members and report the case. Subjects and Methods. Data collection was based on medical records, family history, karyotype analysis, and FISH analysis. Results. The karyotype of the proband revealed mos 49, XXXXY[45]/46, XY[5]. The patient's mother is affected by mosaic Turner Syndrome low level and the maternal grandmother by inversion of chromosome 9. The father, the younger brother, and the paternal grandmother present variations in the normality of their chromosomes. Conclusions. It is important to highlight that the early diagnosis of the syndrome and the initiation of therapy reduce biopsychosocial impairment. Investigation of other family members makes genetic counseling more effective.

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are found in familial isolated pituitary adenoma syndrome (FIPA) families and in a small number of sporadic pituitary adenoma (PA) patients. Although the tumorigenic mechanisms of AIP mutations are unclear, truncating mutations are considered pathogenic, but missense mutations are difficult to evaluate. p.R16H (c.47G>A) is a controversial AIP variant of unknown significance. Aim: To describe a new PA case associated with AIP p.R16H. Patients and methods: One AIP p.R16H non-functioning pituitary adenoma (NFPA) case identified by mutation sequencing screening of sporadic PA patients; 108 controls were screened for p.R16H. Results: The 38 yrs. old male NFPA patient had no family history of PA and harboured a heterozygous p.R16H variant. The proband and two brothers presented severe intellectual disability. Severe visual impairment was the initial symptom and clinical, biochemical and imaging examination demonstrated a large NFPA invading the right cavernous sinus. After transsphenoidal debulking, the remaining tumor continued growth. One of proband’s sisters was negative for p.R16H. Among controls, we identified one heterozygous p.R16H carrier, presenting a thyroid follicular neoplasm. Loss of heterozygosity analysis of the pituitary and thyroid tumors was not performed. Conclusions: We report two new occurrences of AIP p.R16H, associated with a NFPA and with a thyroid tumor. The NFPA patient was young and presented an invasive macroadenoma, features typical of AIP-mutated patients. Because the association between p.R16H and PAs has not been conclusively established, further research of p.R16H is warranted, in view of its implications for AIP genetic testing.

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Severe hypokalemia is a life threatening event, which triggers a number of therapeutic and diagnostic attitudes. In this paper we present a case of 63 years old man, who presented with progressive lassitude, edema, weight loss. The mild hypertension and hyperglycaemia were treated with spironolactone and diet. Initial evaluation showed severe hypokalemia (1.7 mmol/l), hepatomegalia, hyperplasic/nodular adrenal masses; in addition, he has developed a right middle lobe pneumonia which improved with antibiotics. Referred for the suspicion of hyperaldosteronism, aldosterone values were normal (9.3-9.5 ?g/dl), but ACTH was high (725 pg/ml) and did not suppress (710.8 pg/ml) to high dose DXM, as well as cortisol: basal values 27.78 ug/dl, high dose DXM 35.06 ug/dl, showing an ACTH dependent Cushing syndrome despite lack of suggestive clinical signs. Tumor markers suggested a neuroendocrine neoplasia: carcinoembryonic antigen=101 ng/ml (normal values=0.52-6.3 ng/ml), CA 19-9= 155 ng/ml (N < 33 ng/ml). Further radiological evaluation showed a 3 cm right lobe lung tumour. Despite high potassium supplements and spironolactone, the hypokalemia remained around 3.2 mmol/l, characteristic for an apparent mineralocorticoid excess. Because of aggressive evolution of the lung tumour, he died three months after the initial admission into the hospital. Pathology report showed a lung carcinoma. ACTH immunostaining of the lung tumour was positive and revealed a paraneoplastic secretion.

Alteration in nervous system function in patients with thyrotoxicosis is frequent. In rare cases, mental disturbances may be severe: maniac-depressive, schizoid or paranoid reaction. The pathophysiologic basis of these nervous system findings is not well understood. The first patient, being on treatment with benzodiazepine and Risperidone for mood deterioration, was admitted in Thyroid Unit 1 for clinical features suggesting addition, he developed auditory and visual hallucinations, bizarre behavior, disorganized speech, disorientation, poor attention and loss memory for recent events, having a good clinical response after addition of antithyroid drug therapy. The second case developed clinical features suggesting thyrotoxicosis, associated with visual and auditory hallucinations, marked psychomotor agitation and bizarre behavior. After an unsuccessful monotherapy (Risperidone), a good response of clinical features (including psychiatric symptoms) to combined therapy (Methimazole and Risperidone) was recorded. The diagnosis of Graves&#8217; disease was based on clinical and laboratory data (suppressed serum TSH level, elevated serum FT3) and ophthalmological examination or positive anti - TPO antibodies. Both patients were successfully treated with combined therapy - Methimazole and Risperidone. Both case reports demonstrate the importance of performing thyroid function tests in patients with acute psychosis.

Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid\r\ndedifferentiation. Rarely, ATC associates rhabdoid characteristics and only few cases have been\r\npresented to date. We present a case of a thyroid papillary carcinoma which shifted to an\r\naggressive anaplastic form with rhabdoid dedifferentiation and concomitant leukemic reaction\r\nwith eosinophilia. A 76 years old man with a long standing history of a thyroid nodule, noticed\r\nwithin months a rapid growth of the nodule associating marked compression phenomena with\r\nleft deviation of the trachea and esophagus and mild dysphonia. Palliative surgery was\r\nperformed, but the evolution was unfortunate with further health deterioration (fatigue, dyspnea,\r\ndysphagia, loss of appetite and weight loss). Laboratory tests proved leukocytosis with\r\nneutrophilia and left deviation of leukocytes formula, with major eosinophilia. The pathology\r\nshowed a thyroid papillary carcinoma with anaplastic changes. By immunohistochemistry,\r\nit was confirmed the thyroid origin of the tumor (thyreoglobulin positive areas) but also the\r\nepithelial nature of the undifferentiated areas (positive areas for cytokeratin and epithelial\r\nmembrane antigen). Moreover, in the anaplastic areas, rhabdoid differentiation was\r\nidentified by positive coloration against vimentin, protein S100 and desmin. The tumor was\r\naggressive by its anaplastic transformation, confirmed by a high proliferation index (Ki67:\r\n40% positive). The computed tomography was concordant with the phenotype predicted by\r\nhistological description showing a malignant thyroid tumor, invading cervical and mediastinal\r\nareas with secondary lung disseminations. Unfortunately, the outcome was fatal even though\r\nadditional treatment methods have been tried: radiotherapy and chemotherapy. The\r\nparticularities of this case reside in the very rare dedifferentiation of a papillary thyroid\r\ncarcinoma towards an anaplastic thyroid carcinoma harboring the rhabdoid phenotype and\r\nalso its association with eosinophilia.

Abstract Context. Autoimmune progesterone dermatitis (AIPD) is a rare, cyclical dermatosis, with variable clinical presentation, occurring exclusively or being aggravated during the luteal phase of the menstrual cycle, when levels of progesterone rise. Its pathogenesis is still unclear. AIPD is thought to occur as an autoimmune reaction to endogenous possibly modified progesterone, but it could also be triggered by exogenous progesterone exposure. AIPD is a diagnosis of exclusion. Usually there is no or limited response to oral H1 antihistamines and a partial response to steroids. Ovulation inhibitors represent the specific treatment. Case report. We report a case of AIPD in an 18-year-old nulliparous patient with no medical history of allergic diseases and no exposure to oral contraceptive pills. AIPD was suspected based on the clinical picture (recurrent cyclical eczematous eruption on the face and abdominal area) and confirmed by positive intradermal test and positive progesterone challenge. This diagnosis was supported by the result of the skin biopsy, which also helped to exclude other dermatoses with premenstrual aggravation. The rash responded satisfactorily to treatment with a combination of oral contraceptives, levonorgestrel and estrione, which is currently considered first line therapy. Conclusions. This case is of particular interest due to the lack of previous pregnancy or exposure to progesteron therapy. Recurrent, cyclical eruptions in fertile women should raise the suspicion of AIPD. If early recognized, the patient may benefit from non-invasive treatment that improves significantly the quality of life.

Introduction.Cardiomyopathy secondary to severe hypocalcaemia can lead to death when misdiagnosed. However, it can respond favorably to calcium and vitamin D as in this observation.\r\nCase report. SB, 50 years old, was hospitalized for heart failure. He was operated on for cataracts and treated for epilepsy, but was not known as having heart problems.\r\nClinical examination revealed global heart failure. Chest x ray showed cardiomegaly with bilateral pleural effusion. Echocardiography demonstrated myocardium dilatation with an\r\nimpaired systolic function (ejection fraction = 38%, N&#8805; 60). Heart screening did not find any cause, but laboratory investigation diagnosed severe hypocalcemia (mean value: 26mg/L (N=80-105) or 0.65 mmol/L), high phosphorus (61.5mg/L, N=25-45), and low parathormone (6.51 pg/mL, N=15-65 pg/mL). Corrected calcium according to protidemia\r\nwas 0.69 mmol/L. Magnesium was normal. Brain CT scan showed bilateral and symmetrical calcifications of basal ganglia\r\narguing for Fahr?s syndrome. After calcium (1g) and vitamin D (2, then 3 &#956;g/day) during one week, cardiac abnormalities improved promptly. Three months later seizures disappeared totally after stopping anti epileptic drugs.\r\nConclusion.The fast reversibility of heart failure and seizures under calcium suggests observed symptoms were due to hypocalcaemia, seemingly installed on a previously normal heart function. So, calcium assessment should be checked systematically in heart insufficiency.

Context. Rapidly progressive precocious puberty (RPPP) is a rare condition in Turner syndrome (TS), with no consensus on treatment and follow-up. Only 12 cases have been reported so far. Objective. We aimed to evaluate the effects of the GnRH analog (GnRHa) on growth and anti-mullerian hormone (AMH) levels in TS and RPPP. Design. The clinical and laboratory data was recorded at baseline and after treatment. Subjects and methods. An 8.1-year old girl with a karyotype of 45, X/46, XX presented with breast development at Tanner stage-2. Breast development advanced to Tanner stage-3 at the age of 8.7 years. Growth velocity (GV) was 8 cm/year. Bone age was 11 years with a predicted adult height of 152 cm. Luteinizing hormone (LH) was 1.69mIU/mL and estradiol was 33pg/mL, confirming the central puberty. AMH level was 6.33ng/mL. The sizes of ovaries and uterus were compatible with the pubertal stage, with an endometrial thickness of 5 mm. GnRHa was started for RPPP. Results. After three months, GV declined to 0 cm/3 months and AMH level to 50% of the baseline. Growth hormone (GH) treatment was started for insufficient growth. GV improved with GH treatment, as well as a far more decreased AMH level. Conclusion. GV usually declines before puberty in patients with TS, even if the mid-parental height is tall. RPPP should be considered if GV is increased. Excessive suppression of growth may be prevented with GH treatment. GnRHa treatment also plays a role in reducing AMH levels in patients with TS.

Introduction. This case report is the fourth of its type in the medical literature. It describes total thyroidectomy for recurrent relapses of Graves encephalopathy (GE) despite medical treatment. Case presentation. A 33-year-old male presented with impaired consciousness and convulsions. He had postthyroid surgery recurrent Graves’ disease with a goitre. Based on this fact, high thyroid antibodies titres and the exclusion of other causes of such neurological manifestations, he was diagnosed to have GE. This is a rare variant of “encephalopathy associated with autoimmune thyroid disease” (EAATD). Despite the administration of steroid therapy and other standard therapeutic measures, he developed five relapses within 17 months. Total thyroidectomy was advised. Unfortunately, he got another severe attack that required intensive care admission. After three days of discharging, he had urgent total thyroidectomy. The operation went well and for 18 months’ follow-up he had no more attacks. However, thyroid antibodies remained high. Discussion. The report provides details on the diagnosis, standard management and the indication for thyroidectomy for GE. It describes its challenges, precautions, technique and outcomes. It reviews the extent of surgery as well as the clinical and antibody outcomes of the previous three related reports, in comparison with the current one. Conclusion. For medically uncontrolled relapse of GE, thyroidectomy consistently results in ending the attacks. It, therefore, should be put in more consideration in the treatment protocols. On the other hand, one should not depend on antibody levels as a measure of treatment success.