Glycemic State in Diabetic Patients during the Post-Stroke Recovery Phase.

Background: Hyperglycemia is common in the early acute stroke phase especially in patients with diabetes. To the best of our knowledge, no study has evaluated the course of hyperglycemia in patients with diabetes during the post-stroke recovery phase. Methods: It was an observational study conducted in Tabassom Rehabilitation Center for Stroke Patients, Tehran, Iran, 2018-2021. Forty-seven consecutive patients with diabetes and stroke were enrolled and included if at least 3 months had passed from their stroke . Any change in glycemic control before and after stroke was controlled by monitoring drugs used for diabetes treatment and laboratory results. To assess categorical variables, the Pearson chi-squared test was used. Quantitative variables before and after the stroke were analyzed by the paired sample t-test. Results: The mean age was 63.6 ± 6.9 years, and 22 patients were women. The median time from occurrence of stroke to the first visit was 5 months and 6 days. Glycemic control improved among patients with diabetes during the post-stroke recovery phase. There was a significant decrease of 0.7 ± 1.3 % in HbA1c (P = 0.001). The number and the dose of drugs needed for diabetes treatment decreased. No significant correlation could be found between changes in HbA1c and weight. Conclusion: Despite the initial increase in glycemia in patients with diabetes in the acute phase of stroke, glycemic control improves after stroke, and often, it is necessary to decrease diabetes drugs to prevent hypoglycemia. This topic is important and should be addressed by guidelines and institutions involved in the care of patients with diabetes and stroke.

Clinical and Laboratory Characteristics of a Large Iranian Kindred Afflicted with Von Hippel Lindau Disease.

BACKGROUND: Von Hippel Lindau (VHL) disease is a hereditary disorder characterized by the development of benign or malignant tumors in the brain, spinal cord, eyes, adrenal medulla, kidney, pancreas, and many other organs. Advances in molecular diagnosis have led to the identification of the affected members of families at earlier stages. We present the clinical, laboratory, and genetic characteristics of five generations of a large Iranian kindred with VHL. METHODS: The proband, a 52-year-old Iranian man, was recognized with VHL. All family members underwent clinical, laboratory, imaging, and genetic evaluation. Medical files and histopathology reports of patients who had been operated on before were also reviewed. Diagnosis of the disease was based on clinical findings, positive family history of VHL, and development of a central nervous system or retinal hemangioblastoma or pheochromocytoma. RESULTS: Based on diagnostic criteria, our initial evaluations revealed that 10 members of the family had already been affected by the disease. Among them, nine had pheochromocytoma, and one had retinal hemangioblastoma. There was no case of kidney tumors among the kindred. CONCLUSIONS: Study results show the high penetrance of the disease and focus on the large burden imposed by the disease on the health and quality of life of patients afflicted with the disease, emphasizing the importance of surveillance from early childhood for detection and management of the disease as early as possible.

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma

SUMMARY Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma.

Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

IgG4-related hypophysitis.

Hypophysitis is a rare pituitary inflammatory disorder classified in different ways. Immunoglobulin G4-related disease (IgG4-RD), also a rare disease is a systemic fibro-inflammatory condition characterized by infiltration of tissue with IgG4-positive plasma cells; however prevalence of both of them probably is underestimated. In this paper, we present an Iranian patient with biopsy-proven IgG4-related hypophysitis and then review the clinical characteristics, laboratory, imaging, pathologic findings and therapeutic management as well as prognosis of 115 published cases of hypophysitis secondary to IgG4-related disease.

Ectopic cushing's syndrome due to corticotropin releasing hormone.

Cushing's syndrome (CS) secondary to corticotropin releasing hormone (CRH) producing tumors is rare. In this paper we present an Iranian patient who was admitted to our hospital with classic signs and symptoms of CS. Laboratory evaluation revealed high serum and urine cortisol which could not be suppressed with dexamethasone. Abdominal CT scan revealed a mass in abdominal cavity. A percutaneous needle biopsy was performed and histopathologic evaluation revealed that the mass was a neuroendocrine tumor. A multi-disciplinary approach including resection of the mass, bilateral adrenalectomy somatostatin analogue and chemotherapy was applied for management of the disease. Extensive review of English literature focusing on the topic from 1971 to 2018 revealed that there have been only 75 similar cases. Clinical, laboratory, imaging, histopathologic characteristics and managements of these patients will also be discussed in this paper.

Hereditary Vitamin D Resistant Rickets: Clinical, Laboratory, and Genetic Characteristics of 2 Iranian Siblings.

PURPOSE AND METHODS: Hereditary vitamin D resistant rickets (HVDRR) is a rare disease that presents with signs and symptoms of rickets, alopecia, and growth retardation during the early years of life. The disease is caused by mutations in the vitamin D receptor (VDR) gene, which leads to unresponsiveness of the mutant receptor to 1-25(OH) 2 D3. The disease is transmitted as an autosomal recessive disorder and is found with equal frequency in males and females. The disease is rarely encountered and only about 100 cases are reported so far. The current paper reported the clinical and laboratory characteristics of 2 Iranian siblings with this disorder. RESULTS AND CONCLUSION: They presented with rickets, growth retardation, muscle weakness, hypocalcemia and alopecia totalis since early childhood, and were followed up for 27 years. Sequencing of the DNA extracted from the peripheral white blood cells showed a missense G to A mutation in exon number 4 (g.30994 G > A) that led to the methionine substitution for the naturally occurring valine at position 26 in the DNA binding domain (DBD) of the VDR.

Hypocalcemia and osteomalacia after bariatric surgery.

INTRODUCTION: Obesity has become a major health problem not only in industrialized societies but also in developing countries. Multiple studies have shown that bariatric surgery has been effective in reducing substantial amount of weight and also the comorbidities and is being performed more frequently as an established treatment. Due to anatomical and physiological alterations after surgery that impairs absorption of vitamin D and calcium, two fundamental factors in bone formation, their intestinal absorption is highly compromised. CASE REPORT: We present a 48-year-old woman who was visited in emergency room for generalized bone pain, perioral paresthesia and carpopedal spasm. She had undergone bariatric surgery 15 years ago. Chvostek's sign and Trousseau's sign were positive. Examination of thoracic ribs elicited severe pain on palpation. Laboratory evaluation revealed: Ca = 6.1 mg/dL, P= 2.1 mg/dL, alkaline phosphatase = 432 (160-303), PTH=541 pg/mL, and 25(OH)D3= 3 ng/mL. Whole body bone scan showed increased uptake in the anterior arc of left 6th rib, posterior arc of left 6th and 12th ribs with increased uptake of costochondral joints. CONCLUSION: Our case highlights the possible consequences that bariatric surgery may have on bone and mineral health and the need for regular and proactive follow-up of the patients.

A survey of clinical practice patterns in diagnosis and management of Cushing's disease in Iran.

BACKGROUND: Cushing's disease is the most prevalent cause of endogenous adrenocorticotrophic hormone hypersecretion. The aim of this study was to document the current clinical practice pattern in the management of Cushing's disease by Iranian Endocrinologists to determine their opinions and compare them with the current clinical practice guidelines. METHODS: An eight-item questionnaire dealing with diagnosis, treatment and follow up of patients with Cushing's disease was developed, piloted, and sent to the members of Iranian Endocrinology Society. RESULTS: Among 90 endocrinologists invited to participate in the survey, 76 replied. Most respondents selected overnight dexamethasone suppression test (ONDST) and assessment of 24-hour urinary free cortisol (UFC) as the best screening tests followed by midnight serum cortisol and midnight salivary cortisol. Classic high dose dexamethasone suppression test and measurement of serum ACTH were selected for localization of the primary lesion by 64.5%. The primary choice of treatment was trans-sphenoidal pituitary surgery (86.8%). For the recurrence of Cushing's disease, the preferred treatment modality was medical therapy followed by bilateral adrenalectomy, and pituitary re-surgery. In case of treatment failure after the first pituitary surgery and ketoconazole treatment, 51% chose bilateral adrenalectomy, while36.8% selected pasireotide only. CONCLUSION: ONDST and UFC are two most common tests used to screen an index case with signs and symptoms of hypercortisolism. The primary choice of treatment in Cushing's disease is pituitary surgery. However, medical treatment by ketokonazol is preferred for the recurrences. Pasireotide is the second alternative after bilateral adrenalectomy in case of treatment failure after pituitary surgery and ketoconazole.

A Woman with Normotensive Primary Hyperaldosteronism.

Normotensive hyperaldosteronism is a rare disorder. It is usually diagnosed with hypokalemia or an adrenal mass. Our patient was a 27-year-old female presented with weakness. She had normal blood pressure, hypokalemia, high plasma aldosterone level and suppressed plasma renin activity. After the saline load, test aldosterone didn't show suppression. Adrenal computed tomography revealed a left adrenal mass. The patient was treated with spironolactone and potassium supplement. Surgical adrenalectomy was done. Final pathologic diagnosis was benign adrenocortical adenoma without capsular invasion. In postoperative course serum, potassium was normal.

Ectopic Cushing's syndrome secondary to lung and mediastinal tumours -- report from a tertiary care centre in Iran.

INTRODUCTION: Ectopic Cushing`s syndrome (ECS) secondary to neuroendocrine tumours (NETs) of the lung and mediastinum are rarely encountered. In this study, we present our experience in Iran on 15 patients with ECS secondary to lung and mediastinal tumours over a period of 27 years. MATERIAL AND METHODS: Since 1985, 15 patients with ECS secondary to lung and mediastinal tumours have been diagnosed and prospectively followed by the endocrinology team of Taleghani Hospital, Tehran, Iran. The clinical signs and symptoms, laboratory findings, radiological features, immunohistochemical characteristics, management strategies and outcome data are here presented. RESULTS: There were six women and nine men, aged 26-70 years, all presenting with typical features of Cushing's syndrome. Based on histopathologic evaluations, four patients had small cell lung cancer (SCLC) and seven patients had pulmonary NETs, one patient had a thymic NET, and one case was diagnosed as a lung tumourlet. The mean ± SD serum cortisol, 24h urine free cortisol and plasma ACTH were 47.2 ± 20.5 µg/dL, 2,702 ± 5,439 µg/day, and 220 ± 147 pg/mL, respectively. Pulmonary lesions ranged in diameter from 1.1 to 4 cm (mean 1.9 ± 1.1 cm). One patient had a 10 cm mediastinal mass. The duration of follow up in these cases was between one month and seven years (mean 29.9 ± 27.5 months). The four patients with SCLC died within three months of diagnosis. CONCLUSION: Our data demonstrates the protean clinical and laboratory manifestations of ECS secondary to lung and mediastinal tumours, the problems encountered in diagnosis, and the need for a multidisciplinary approach. This study confirms other series from Western Europe and North America that, unlike the SCLC patients who show a poor outlook, ECS secondary to lung carcinoids has a more favourable prognosis.

Treatment of invasive silent somatotroph pituitary adenoma with temozolomide. Report of a case and review of the literature.

Improved imaging techniques have contributed to increased diagnosis of pituitary tumors. These tumor types can be microadenomas or macroadenomas and can either be functional or non-functional. Atypical or aggressive pituitary adenomas are tumors that rapidly increase in size and may invade into the suprasellar or parasellar regions. They are characterized by a Ki-67 nuclear labeling index greater than 10 %. Management of these tumors is difficult, and many recur after surgery. Temozolomide, a second generation alkylating agent, has been showing promising results in the treatment of these tumors. The patient was a 39-year-old male diagnosed with an invasive silent somatotroph pituitary macroadenoma treated with temozolomide after surgery. We present the case along with the review of the literature of the therapeutic effects of temozolomide in somatotroph macroadenomas.

Absence of association between vitamin D deficiency and incident metabolic syndrome: Tehran Lipid and Glucose Study.

BACKGROUND: Links between vitamin D status and metabolic syndrome have been reported in cross-sectional studies; however, few prospective studies regarding this association exist. We performed this study to assess prospective association between vitamin D status and incident metabolic syndrome in a large population-based cohort. METHOD: This was a nested case-control study within the Tehran Lipid and Glucose Study (TLGS) which followed representative Tehranian adults. A total of 324 matched pairs aged 20 or older were selected. Cases and controls were free of metabolic syndrome according to definition of Joint Interim Statement (JIS) at baseline and followed for a mean duration of 6.8 years. Each case was matched individually by sex, age, duration of follow-up, and month of entry to the study with a randomly selected control. Prespecified cut points were used to characterize varying degrees of 25-hydroxyvitamin D [25(OH)D] deficiency (<20, 20-29.9, and ≥30 ng/mL). Conditional logistic regression was used to investigate the association between 25(OH)D concentration and the incident metabolic syndrome. RESULTS: The mean age of participants was 40.8±11.7, and 50% were women. The median [interquartile range (IQR) 25-75] of serum 25(OH) D was 16 ng/mL (10-25 ng/mL) and there was no difference between cases (16 ng/mL; IQR 10-25 ng/mL) and controls (16 ng/mL; IQR 10-26 ng/mL). The odds ratio of serum 25(OH)D <20 ng/mL for developing metabolic syndrome was 0.97 [95% confidence interval (CI) 0.6-1.52] compared with serum 25(OH)D ≥30 ng/mL. Adjustment for potential confounders did not change the results. CONCLUSIONS: Our study does not provide evidence that there is association between different serum vitamin D levels and incidence of metabolic syndrome.

Functioning adrenocortical tumors in children-secretory behavior.

OBJECTIVE: Adrenocortical tumors are rare childhood neoplasms. More than 95% are functional and present with virilization, Cushing's syndrome, hypertension, or hyperestrogenism. The objective of this paper is to present the clinical, laboratory and pathological findings of this rare disease and to highlight the secretory behavior of these tumors. METHODS: Clinical and laboratory data of seven Iranian children and adolescents aged between 2 and 16 years with functioning adrenocortical tumors are presented. Five patients had virilization and two had Cushing's syndrome at the time of diagnosis. In all subjects, the tumors were removed successfully by open surgery, during which a blood sample was drawn from the corresponding adrenal vein for hormonal evaluation. RESULTS: Peripheral blood evaluation revealed that in addition to the dominant hormone (testosterone in the cases presenting with virilization and cortisol in those with Cushing's syndrome), significant amounts of other hormones were secreted from these tumors. Adrenal vein evaluation revealed that testosterone, dehydroepiandrosterone sulfate, estradiol, 17(OH) progesterone, and cortisol were directly released from the tumor. The tumors weighed between 36-103 grams. The patients have since been followed for 5 to 20 years, and there have been no signs or symptoms of relapse in any of the patients. CONCLUSIONS: The study shows that functioning adrenocortical tumors should be considered in children and adolescents presenting with hyperandrogenism, Cushing's syndrome, or hyperestrogenism. A diagnosis of a functioning adrenocortical tumor requires surgical removal as early as possible to prevent the untoward effects of virilization or corticosteroid excess. Evaluation of adrenal vein hormones showed that the steroids are secreted directly from the tumor and peripheral conversion has little contribution to the serum levels.

Ectopic acromegaly due to growth hormone releasing hormone.

Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing hormone (GHRH) is rarely encountered. We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma. Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas. We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression. Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs. The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly. Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long-term morbidity and mortality with ectopic acromegaly.

Cushing syndrome secondary to a thymic carcinoid tumor due to multiple endocrine neoplasia type 1.

OBJECTIVE: To present an Iranian patient with a nonclassic form of multiple endocrine neoplasia type 1 (MEN 1) who presented with ectopic Cushing syndrome (CS) secondary to a corticotropin (ACTH)-producing thymic neuroendocrine tumor (NET), recurrent renal stones, and a giant cell granuloma of the jaw due to primary hyperparathyroidism (PHPT) without involvement of the pituitary or pancreas. METHODS: Relevant imaging and hormonal evaluations were performed. The patient was operated on 2 occasions for a thymic NET and on 3 occasions for PHPT. DNA from a peripheral blood sample was extracted for sequencing of the MEN1 gene. RESULT: Histopathologic evaluation of the thymic tumor removed during the first surgery showed an atypical carcinoid tumor with a Ki-67 labeling index of 5%. Evaluation after the second surgery revealed an invasive carcinoid tumor with a Ki-67 labeling index of 30%. Parathyroid pathology was suggestive of glandular hyperplasia. Menin gene sequencing revealed a novel frameshift mutation c.1642_1648dup in exon 10. CONCLUSION: This case of MEN 1 is unusual because most thymic NETs in MEN 1 are nonfunctional, and secretion of ACTH or other ectopic hormones rarely occurs. In patients presenting with thymic NETs, the possibility of MEN 1 should be considered, especially in the presence of hyperparathyroidism. This case also demonstrates that the behavior of thymic NETs can change over time from slow-growing tumors to highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN 1.

N-acetylcysteine does not prevent contrast-induced nephropathy after cardiac catheterization in patients with diabetes mellitus and chronic kidney disease: a randomized clinical trial.

BACKGROUND: Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) constitute to be a high-risk population for the development of contrast-induced nephropathy (CIN), in which the incidence of CIN is estimated to be as high as 50%. We performed this trial to assess the efficacy of N-acetylcysteine (NAC) in the prevention of this complication. METHODS: In a prospective, double-blind, placebo controlled, randomized clinical trial, we studied 90 patients undergoing elective diagnostic coronary angiography with DM and CKD (serum creatinine > or = 1.5 mg/dL for men and > or = 1.4 mg/dL for women). The patients were randomly assigned to receive either oral NAC (600 mg BID, starting 24 h before the procedure) or placebo, in adjunct to hydration. Serum creatinine was measured prior to and 48 h after coronary angiography. The primary end-point was the occurrence of CIN, defined as an increase in serum creatinine > or = 0.5 mg/dL (44.2 micromol/L) or > or = 25% above baseline at 48 h after exposure to contrast medium. RESULTS: Complete data on the outcomes were available on 87 patients, 45 of whom had received NAC. There were no significant differences between the NAC and placebo groups in baseline characteristics, amount of hydration, or type and volume of contrast used, except in gender (male/female, 20/25 and 34/11, respectively; P = 0.005) and the use of statins (62.2% and 37.8%, respectively; P = 0.034). CIN occurred in 5 out of 45 (11.1%) patients in the NAC group and 6 out of 42 (14.3%) patients in the placebo group (P = 0.656). CONCLUSION: There was no detectable benefit for the prophylactic administration of oral NAC over an aggressive hydration protocol in patients with DM and CKD. TRIAL REGISTRATION: NCT00808795.