DICER1 Syndrome in Twins With Ovarian Sertoli-Leydig Cell Tumor and Papillary Thyroid Carcinoma.

DICER1 syndrome is a rare autosomal dominant syndrome resulting in benign and malignant tumors in various organs with tumors in endocrine organs (pituitary, thyroid, adrenal, ovaries, and pancreas). Here we present a rare case of 18-year-old twin sisters with DICER1 syndrome who presented at the age of 15 years with hirsutism, deepening of the voice, and amenorrhea. They were diagnosed with a Sertoli-Leydig cell tumor of the ovary and underwent unilateral oophorectomy, with no evidence of recurrence or metastasis during follow-up. Genetic analysis showed the same germline DICER1 mutation in both cases. They also had large multinodular goiters (nodule size ranging from 1.0 to 2.3 cm) nodules were increasing in size. Fine needle aspiration cytology (FNAC) of thyroid nodules for both the sisters showed atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), and they both underwent total thyroidectomy revealing papillary thyroid carcinoma. No pituitary lesion was observed in the brain magnetic resonance imaging (MRI) of either of them. A chest CT scan showed bilateral sub-pleural benign-looking nodules in both patients. The twin sisters developed some features, such as Sertoli-Leydig cell tumor, multinodular goiter, and papillary thyroid carcinoma, and had positive genetic tests for DICER1 germline mutation. The father and paternal grandfather had a family history of papillary thyroid carcinoma. Both patients require active surveillance due to the increased risk of developing tumors in multiple organs associated with this disease.

Management of Diabetes Insipidus following Surgery for Pituitary and Suprasellar Tumours.

Central diabetes insipidus (CDI) is a common complication after pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an abnormally large volume of dilute urine with increasing serum osmolality. The reported incidence of CDI after pituitary surgery ranges from 0-90%. Large tumour size, gross total resection and intraoperative cerebrospinal fluid leak usually pose an increased risk of CDI as observed with craniopharyngioma and Rathke's cleft cysts. CDI can be associated with high morbidity and mortality if not promptly recognised and treated on time. It is also essential to rule out other causes of postoperative polyuria to avoid unnecessary pharmacotherapy and iatrogenic hyponatremia. Once the diagnosis of CDI is established, close monitoring is required to evaluate the response to treatment and to determine whether the CDI is transient or permanent. This review outlines the evaluation and management of patients with CDI following pituitary and suprasellar tumour surgery to help recognise the diagnosis, consider the differential diagnosis, initiate therapeutic interventions and guide monitoring and long-term management.

Contemporary Management of Clinically Non-functioning Pituitary Adenomas: A Clinical Review.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumours that constitute about one-third of all pituitary adenomas. They typically present with symptoms of mass effects resulting in hypopituitarism, visual symptoms, or headache. Most NFPAs are macroadenomas (>1 cm in diameter) at diagnosis that can occasionally grow quite large and invade the cavernous sinus causing acute nerve compression and some patients may develop acute haemorrhage due to pituitary apoplexy. The progression from benign to malignant pituitary tumours is not fully understood; however, genetic and epigenetic abnormalities may be involved. Non-functioning pituitary carcinoma is extremely rare accounting for only 0.1% to 0.5 % of all pituitary tumours and presents with cerebrospinal, meningeal, or distant metastasis along with the absence of features of hormonal hypersecretion. Pituitary surgery through trans-sphenoidal approach has been the treatment of choice for symptomatic NFPAs; however, total resection of large macroadenomas is not always possible. Recurrence of tumours is frequent and occurs in 51.5% during 10 years of follow-up and negatively affects the overall prognosis. Adjuvant radiotherapy can decrease and prevent tumour growth but at the cost of significant side effects. The presence of somatostatin receptor types 2 and 3 (SSTR3 and SSTR2) and D2-specific dopaminergic receptors (D2R) within NFPAs has opened a new perspective of medical treatment for such tumours. The effect of dopamine agonist from pooled results on patients with NFPAs has emerged as a very promising treatment modality as it has resulted in reduction of tumour size in 30% of patients and stabilization of the disease in about 58%. Despite the lack of long-term studies on the mortality, the available limited evidence indicates that patients with NFPA have higher standardized mortality ratios (SMR) than the general population, with women particularly having higher SMR than men. Older age at diagnosis and higher doses of glucocorticoid replacement therapy are the only known predictors for increased mortality.

Clinical Features, Therapeutic Trends, and Outcome of Giant Prolactinomas: A Single-Center Experience Over a 12-Year Period.

BACKGROUND: Management of giant prolactinomas presents a different challenge than the management of traditional prolactinomas. OBJECTIVE: The aim of this study was to report the largest long-term single-center study of giant prolactinomas to analyze their clinical features; define epidemiological characteristics, comorbidities, complications, treatment outcomes; and to demonstrate our experience with long-term cabergoline (CAB) treatment of these giant tumors. METHODS: A retrospective case study and clinical review of patients presenting with giant prolactinomas in the pituitary clinic at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, in the period between 2006 and 2018 were included in the study. Of the charts reviewed, 33 patients (24 men; 9 women) with age of diagnosis between 18 and 63 years (mean = 37.21 years) met the selection criteria for giant prolactinomas. RESULT: The most common presenting features include headache (87.8%), visual defects (69.7%), and hypogonadism (51.5%). The baseline means serum prolactin (PRL) level was extremely high for both sexes (95 615.03 nmol/L), which eventually decreased by as much as 95.4% after CAB treatment. Serum PRL concentrations completely normalized in 11 patients and significantly reduced in 22 patients. The mean tumor volume at baseline was 42.87 cm3, whereas the mean posttreatment tumor volume was 3.42 cm3 (no residual tumor in 2 patients, while in others, it ranged from 0.11 to 16.7 cm3) at the last follow-up visit. The mean change in tumor volume was 88.84%. Tumor volume decreased by an average of 92% for men and 80.4% for women. One patient had no tumor size change with CAB (3.5 mg thrice a week) or radiotherapy and required surgery. The response rate (remission after medical therapy alone) in this series was 84.84%. CONCLUSIONS: Findings reinforce results from our previous study that CAB provides dramatic clinical improvements with an excellent safety profile. The CAB should, therefore, be considered as the primary therapy for giant prolactinomas.

Clinical features and therapeutic outcomes of patients with acromegaly in Saudi Arabia: a retrospective analysis.

BACKGROUND: Acromegaly is a rare disease resulting in clinical sequelae with significant morbidity and mortality due to the central tumor mass effect and prolonged growth hormone (GH) hypersecretion. OBJECTIVES: The goal is to describe the epidemiology, clinical features, presence of comorbidities, and treatment outcomes of acromegaly in Saudi Arabia. METHODS: Data was collected through a retrospective review of the charts of all patients diagnosed with acromegaly from nine major hospitals in Saudi Arabia over a period of more than 25 years. RESULTS: A total of 195 patients (116 males and 79 females), with a mean age at diagnosis of 43 ± 12 (males) and 46 ± 14 years (females), from nine major hospitals were identified and included in the analysis. All cases were caused by pituitary adenomas, of which 92.4% were macroadenomas. Headache, coarse facial features, acral growth, and sweating/oily skin were by far the most frequent presenting complaints. The most common comorbidities were diabetes mellitus (51.7%), followed by hypertension (50%) and visual field defect (30.5%). The vast majority (95%) of patients were treated surgically (98%). Twenty-four percent also received radiotherapy, and 74.4% received medical therapy. When stringent criteria were applied for assessment of outcomes of therapy, 28.7% of the patients were cured and 30.1% had their disease under control, while 28.7% were found to have active disease despite receiving multimodal therapy. CONCLUSIONS: Our findings highlight the need for a national acromegaly registry to enable early identification, evaluation, and selection of the best therapeutic approaches to improve the outcome and remission rate of the disease.

Management of acromegaly: an exploratory survey of physicians from the Middle East and North Africa.

BACKGROUND: Worldwide variations exist in the diagnosis and management of patients with acromegaly. For such a rare condition, the knowledge and perception of physicians would most likely direct the care of patients. However, the adherence of physicians in non-Western regions to guidelines for the diagnosis and management of acromegaly has not been previously ascertained. METHODS: An online survey was conducted to assess the perceptions and practice of physicians regarding acromegaly diagnosis and management as per international guidelines. An electronic questionnaire containing key questions was mailed, initially to physicians in Saudi Arabia (KSA) and later to other countries in the Middle East and North Africa (MENA) region. Additional questions were included to ensure the relevance of the respondents' replies. The responses were captured and summarized anonymously. Descriptive comparisons were made with two similar international and national surveys from other regions. RESULTS: Two hundred forty-seven doctors responded to the survey. Of these, 155 (64.5%) fulfilled the inclusion criteria and, in particular, confirmed having treated acromegaly patients in the previous 12 months, and they constituted the basis of this study. The three most common referring specialties for patients were internists (44; 28.4%), neurosurgeons (46; 29.6%), and family medicine physicians (42; 27.1%), respectively. The combination of growth hormone (GH) nadir during the oral glucose tolerance test (OGTT) and elevated insulin-like growth factor-1 (IGF-1) levels was used by 99 physicians (63.9%) to diagnose acromegaly. The main determinant for treatment choice was tumor mass characteristics confirmed by 117 respondents (75.5%) with neurosurgery as first treatment choice confirmed by 124 respondents (80%). Combined measurement of IGF-1 and GH levels after OGTT at 3 months after surgery was the most widely used criterion for assessment of surgical outcomes, confirmed by 82 physicians (52.9%). The biggest barriers to optimal management of acromegaly as perceived by 38.1% and 35.5% of the respondents were high cost of medications and lack of physicians' awareness, respectively. CONCLUSIONS: The majority of the surveyed physicians reported variable adherence to the international acromegaly guidelines. Clearly, higher awareness is needed among physicians for early diagnosis and timely referral for specialist management.

Cabergoline-Induced Pneumocephalus Following Treatment for Giant Invasive Macroprolactinoma Presenting With Spontaneous Cerebrospinal Fluid Rhinorrhea.

Cerebrospinal fluid (CSF) rhinorrhea is rarely reported as the first presenting feature of giant invasive macroprolactinomas. Cerebrospinal fluid rhinorrhea is usually reported as a complication of trauma, neurosurgical, and skull-based procedures (such as pituitary surgery or radiations), and less frequently after medical treatment with dopamine agonists (DAs) for macroprolactinomas. This phenomenon results from fistula creation that communicates between the subarachnoid space and the nasal cavity. Meanwhile, pneumocephalus is another well-recognized complication after transsphenoidal surgery for pituitary macroadenomas. This entity may present with nausea, vomiting, headache, dizziness, and more seriously with seizures and/or a decreased level of consciousness if tension pneumocephalus develops. Case reports about the occurrence of spontaneous pneumocephalus after medical treatment with DAs without prior surgical interventions are scarce in the literature. Our index case is a young man who was recently diagnosed with a giant invasive prolactin-secreting pituitary macroadenoma with skull base destruction. A few months before this diagnosis, he presented with spontaneous CSF rhinorrhea with no history of previous medical or surgical treatment. In this case report, we report an uncommon presentation for giant invasive macroprolactinoma with a CSF leak treated with cabergoline that was subsequently complicated by meningitis and pneumocephalus. This is a very rare complication of cabergoline therapy, which occurred approximately 1 month after treatment initiation.

Temozolomide therapy for resistant prolactin-secreting pituitary adenomas and carcinomas: a systematic review.

Pituitary tumors represent 10-15% of all intracranial tumors; of these, prolactinomas account for 40-50% of cases. Prolactinomas usually respond well to dopamine agonists (DA) as first-line therapy. However, treatment resistance remains a concern. Temozolomide (TMZ) is an oral alkylating agent that has shown promise in treating aggressive pituitary adenomas and carcinomas that are resistant to other therapies. To date, no control trials have been undertaken and only single case reports of pituitary tumors treated with TMZ have been published. A systematic literature search was conducted for studies reporting the use of TMZ for the treatment of prolactinomas that were resistant to standard therapy. In total, 42 reported cases were identified and included in our analysis: 23 cases of prolactin-secreting adenomas and 19 of prolactin-secreting carcinomas. Prior to TMZ administration, patients had exhibited tumor progression and had previously undergone various treatments including surgery, radiotherapy, and drug therapy. Tumor shrinkage was reported in 76% of patients. Reduced prolactin levels were observed in 75% of patients, while normalization of prolactin was reported in 8%. TMZ failure occurred in 20.6% of cases. Most patients exhibited no serious adverse effects. In conclusion, TMZ has potential for the treatment of highly aggressive and resistant prolactin-secreting adenomas and carcinomas, as demonstrated by tumor shrinkage or complete response and normalization of hormone hypersecretion, and exhibits good tolerability and few side effects.

Intrathyroidal Parathyroid Cyst: An Unusual Neck Mass.

Parathyroid cyst (PC) is a very rare condition. A case of intrathyroidal PC is being reported here in a 53-year-old woman who presented to the endocrine clinic with slowly progressive painless left anterior neck swelling for 1 year with no symptoms of thyroid or parathyroid dysfunction and no compressive symptoms. Ultrasound of the thyroid showed a well-defined cystic lesion measuring 4.7 × 3.6 cm in maximum diameter with internal echoes within the cyst located in the left lobe of the thyroid gland. Fine needle aspiration revealed colorless clear fluid with a high concentration of parathyroid hormone. The patient underwent left hemithyroidectomy at her request. Histopathology revealed parathyroid tissue with unilocular cyst and thyroid tissue with goitrous changes. She was in remission, and there was no evidence of thyroid or parathyroid dysfunction after surgery.

Slipped Capital Femoral Epiphysis and Primary Hyperparathyroidism: A Case Report.

The aim of reporting this case is to highlight the association of two disorders, primary hyperparathyroidism (PHPT) and slipped capital femoral epiphysis (SCFE). They are usually seen in two different age groups and rarely together. PHPT is a rare cause of SCFE and only 10 cases have been reported in the literature worldwide. The patient in our report is a 13-year-old girl who presented to our clinic with bilateral knee pain and a waddling gait. Subsequent investigations showed that she had PHPT and SCFE with low bone mass. On admission, a parathyroidectomy was performed; then, the slipped femoral epiphyses were fixed with satisfactory results. A systematic algorithmic approach that was illustrated in a previously published case was used. Such cases should be managed with a systematic approach based on the patient's clinical status to prevent future morbidity. A literature review was conducted by performing a Medline search of all reported cases of PHPT and SCFEs.

A Case of Nonfatal Ventricular Arrhythmia Due to Thyrotoxic Periodic Paralysis in a Saudi Patient as an Initial Presentation of Graves' Disease.

Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism characterized by recurrent muscle weakness and hypokalemia. It has been commonly reported in non-Asian populations. Four cases were reported in Saudis so far, and one had a life-threatening arrhythmia. We describe an additional case of a 28-year-old apparently healthy Saudi male patient, who presented with acute paraparesis associated with hypokalemia (K: 2.0 mmol/L), complicated by ventricular tachycardia and cardiac arrest. He was successfully resuscitated and his hypokalemia was corrected. A diagnosis of Graves' disease associated with TPP was made. He was initially treated with carbimazole and ß-blockers and then given a definitive therapy with radioactive iodine, which showed a good response. This case highlights the importance of early recognition and prompt treatment of TPP as a differential diagnosis for muscle weakness. A brief review of TPP and associated arrhythmia is included.