Primary aldosteronism and hypokalemia-induced rhabdomyolysis in a patient with aldosterone-producing adenoma: A case report and literature review.

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

An 81-Year-Old Man Presenting with Asthenia and Anorexia After an Alcohol-Induced Hypoglycemic Coma and a Diagnosis of Central Adrenal Insufficiency: A Case Report.

BACKGROUND Alcohol abuse inhibits the ability of the liver to release glucose into the bloodstream, primarily by inhibiting gluconeogenesis, so chronic alcohol abusers exhibit hypoglycemia after drinking alcohol without eating; this is called alcohol-induced hypoglycemia. Central adrenal insufficiency (AI) is characterized by cortisol deficiency due to a lack of adrenocorticotropic hormone. It is challenging to diagnose central AI, as it usually presents with nonspecific symptoms, such as asthenia, anorexia, and a tendency toward hypoglycemia. Here, we report a rare case of central AI that presented with AI symptoms shortly after an alcohol-induced hypoglycemic coma. CASE REPORT An 81-year-old Japanese man who had been a moderate drinker for >40 years developed a hypoglycemic coma after consuming a large amount of sake (alcohol, 80 g) without eating. After the hypoglycemia was treated with a glucose infusion, he rapidly recovered consciousness. After stopping alcohol consumption and following a balanced diet, he had normal plasma glucose levels. However, 1 week later, he developed asthenia and anorexia. The endocrinological investigation results indicated central AI. He was started on oral hydrocortisone (15 mg/day), which relieved his AI symptoms. CONCLUSIONS Cases of central AI associated with alcohol-induced hypoglycemic attacks have been reported. Our patient developed AI symptoms following an alcohol-induced hypoglycemic attack. His alcohol-induced hypoglycemic attack likely occurred in combination with a developing cortisol deficiency. This case highlights the importance of considering central AI in chronic alcohol abusers presenting with nonspecific symptoms, including asthenia and anorexia, especially when patients have previously experienced alcohol-induced hypoglycemic attacks.

Hypoglycemic Hemiplegia Associated with Reversible Narrowing of the Contralateral Middle Cerebral Artery in a Patient with Adrenal Insufficiency.

A 56-year-old man with a 2.5-month history of anorexia developed sweating, weakness, and left hemiplegia and hemispatial neglect. Brain magnetic resonance imaging detected no abnormalities, but magnetic resonance angiography revealed narrowing of the right middle cerebral artery (MCA). The focal neurological signs and narrowing of the MCA resolved after detection and correction of hypoglycemia. Endocrinological examinations indicated adrenal insufficiency. Hemiplegia is a rare but important neurological manifestation of hypoglycemia, although the mechanisms involved remain unknown. Combined hypoglycemia and decreased MCA blood flow associated with vasospasm probably induced regionally severe neuroglycopenia with ischemia, which presented as focal neurological symptoms.

A 75-Year-Old Woman with a 5-Year History of Controlled Type 2 Diabetes Mellitus Presenting with Polydipsia and Polyuria and a Diagnosis of Central Diabetes Insipidus.

BACKGROUND Central diabetes insipidus (CDI) is a rare disorder characterized by large volumes of dilute urine because of a lack of antidiuretic hormone. Co-existing CDI and diabetes mellitus without inherited disorders such as Wolfram syndrome are rare. It is both important and challenging to diagnose this combination because the 2 conditions present with thirst, polydipsia, and polyuria. A few cases of CDI developing in patients with type 2 diabetes mellitus (T2D) have been reported. We report an unusual case of CDI that developed in an older patient with T2D. The aims of this report are to share the clinical course and discuss clues to the early diagnosis of CDI in T2D. CASE REPORT A 70-year-old Japanese woman developed T2D with hyperglycemia symptoms, including thirst, polydipsia, and polyuria. After starting medical treatment, the hyperglycemia and its symptoms improved. The glycated hemoglobin level decreased from 9% to 6%. However, 5 years later (at 75 years of age), she re-exhibited thirst, polydipsia, and polyuria despite stable glycemic control. Her urine volume was large (6.3 L/day). A urine glucose test was negative. The plasma osmolality was high (321 mOsm/kg), while the urinary osmolality was low (125 mOsm/kg). A significant increase in urinary osmolality following vasopressin administration indicated a diagnosis of CDI. Desmopressin therapy effectively relieved the symptoms. CONCLUSIONS This case highlights the need to consider CDI as a rare but important comorbid disorder in patients with diabetes mellitus, including T2D, particularly those presenting with thirst, polydipsia, and polyuria despite well-controlled glycemia.

Primary Aldosteronism Presenting with Hypertension Five Days after Delivery: A Case Report and Literature Review.

A 35-year-old Japanese woman with no history of hypertension developed hypertension 5 days after normal delivery. Endocrinological and radiological examinations indicated primary aldosteronism (PA) and a 1.4-cm left adrenal tumor. The patient underwent laparoscopic adrenalectomy, and a diagnosis of aldosterone-producing adenoma was confirmed immunohistochemically. Her plasma aldosterone concentration and blood pressure normalized. Cases of PA presenting with hypertension in the postpartum period have been reported. This case suggests that PA should be considered in women with postpartum hypertension, especially in those with blood pressure that suddenly increases shortly after delivery, even if they were normotensive before and throughout pregnancy.

Central Diabetes Insipidus after Syndrome of Inappropriate Antidiuretic Hormone Secretion with Severe Hyponatremia in a Patient with Rathke's Cleft Cyst.

A 49-year-old man developed severe hyponatremia associated with transient headache and was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction and sodium supplementation corrected the hyponatremia. However, several days later, the patient exhibited hypernatremia with thirst and polyuria. A detailed examination indicated central diabetes insipidus (CDI) with an intrasellar cystic lesion indicative of Rathke's cleft cyst (RCC). A case of RCC exhibiting headache, hyponatremia, and subsequent hypernatremia has been reported. Our case shows that CDI may appear after SIADH in patients with RCC, especially in those with serum sodium levels that unexpectedly increase rapidly beyond the reference range.

Isolated Adrenocorticotropic Hormone Deficiency Associated with Severe Hyperkalemia During Pembrolizumab Therapy in a Patient with Ureteral Cancer and an Ileal Conduit: A Case Report and Literature Review.

BACKGROUND Immune checkpoint inhibitors (ICIs) are anticancer medications that enhance the antitumor immune response. The clinical benefit afforded by ICIs, however, can be accompanied by immune-related adverse events (IRAEs). One of the common endocrine IRAEs is hypophysitis, which often causes hypopituitarism with secondary adrenal insufficiency (AI). Secondary AI, including isolated adrenocorticotropic hormone (ACTH) deficiency (IAD), is often associated with hyponatremia. Here, we report an unusual case of ICI-related IAD associated with severe hyperkalemia. CASE REPORT A 78-year-old woman who had an ileal conduit, chronic kidney disease, type 2 diabetes mellitus, and hypertension and was taking an angiotensin II receptor blocker began treatment for advanced ureteral cancer with the anti-programmed cell death protein 1 inhibitor pembrolizumab. The therapy effectively controlled the cancer, but 4 1/2 months after starting it, the patient developed anorexia, general weakness, and muscle pain and was diagnosed with IAD associated with severe hyperkalemia and hyperchloremic metabolic acidosis. She recovered after prompt administration of corticosteroids and treatment with sodium bicarbonate, glucose/insulin, and cation exchange resins. CONCLUSIONS Hyperkalemia is a common symptom of primary AI but is less common in patients with central AI because a lack of ACTH does not cause aldosterone deficiency and mineralocorticoid action is preserved. The present case demonstrates the need for physicians to be aware of severe hyperkalemia as a life-threatening complication of secondary AI induced by ICIs, particularly in patients with predisposing factors, such as kidney dysfunction, diabetes mellitus, an ileal conduit, and renin-angiotensin-aldosterone system inhibitor use.

Prolonged Postoperative Pyrexia and Transient Nonnephrogenic Vasopressin-Analogue-Resistant Polyuria following Endoscopic Transsphenoidal Resection of an Infundibular Epidermoid Cyst.

Prolonged postoperative pyrexia (PPP) due to Mollaret's meningitis following endoscopic transsphenoidal surgery (eTSS) for an intracranial epidermoid cyst can be confused with postoperative meningeal infection after transsphenoidal resection, especially in the middle of the COVID-19 pandemic. Anosmia, as well as dysgeusia, cannot be evaluated in patients of eTSS for a while after surgery. We report a case of an infundibular epidermoid cyst with post-eTSS Mollaret's meningitis (MM). The post-eTSS MM caused vasopressin-analogue-resistant polyuria (VARP) in synchronization with PPP. A 59-year-old man experiencing recurrent headaches and irregular bitemporal hemianopsia over three months was diagnosed with a suprasellar tumor. The suprasellar tumor was an infundibular cyst from the infundibular recess to the posterior lobe of the pituitary, which was gross-totally resected including the neurohypophysis via an extended eTSS. Since awakening from general anesthesia after the gross total resection (GTR) of the tumor, the patient continuously had suffered from headache until the 13th postoperative day (POD13). The patient took analgesics once a day before the surgery and three times a day after the surgery until POD11. Pyrexia (37.5-39.5 degree Celsius) in synchronization with nonnephrogenic VARP remitted on POD18. Intravenous antibiotics had little effect on changes of pyrexia. Serum procalcitonin values (reference range <0.5 ng/mL) are 0.07 ng/mL on POD12 and 0.06 ng/mL on POD18. His polyuria came to react with sublingual desmopressin after alleviation of pyrexia. He left the hospital under hormone replacement therapy without newly added neurological sequelae other than hypopituitarism. After GTR of an infundibular epidermoid cyst, based on values of serum procalcitonin, post-eTSS MM can be distinguished from infection and can be treated with symptomatic treatments. The postoperative transient nonnephrogenic VARP that differs from usual central diabetes insipidus can react with sublingual desmopressin after alleviation of PPP in the clinical course of post-eTSS MM. An infundibular epidermoid cyst should be sufficiently resected in one sitting to minimize comorbidities, its recurrence, or postoperative MM to the utmost.

Isolated Adrenocorticotropic Hormone Deficiency and Primary Hypothyroidism in a Patient Undergoing Long-Term Hemodialysis: A Case Report and Literature Review.

BACKGROUND Patients with end-stage renal disease undergoing long-term maintenance hemodialysis are more likely than the general population to exhibit primary hypothyroidism. Only a few cases of isolated adrenocorticotropic hormone deficiency (IAD) among hemodialysis patients have been reported. We herein report an unusual case of a patient undergoing long-term hemodialysis who exhibited both IAD and primary hypothyroidism. CASE REPORT A 82-year-old male with end-stage renal disease secondary to immunoglobulin A nephropathy, undergoing hemodialysis for 20 years, was found to have primary hypothyroidism without obvious symptoms and consequently began thyroid hormone replacement therapy with oral levothyroxine. At 84 years of age, he developed anorexia, fatigue, and lethargy. A systemic workup using computed tomography and gastrointestinal endoscopy detected no abnormalities. He did not exhibit electrolyte imbalances, such as hyponatremia or hyperkalemia, and had normal morning blood levels of cortisol and adrenocorticotropic hormone. However, he exhibited hypoglycemic coma 4 months later. Detailed endocrinological examinations using dynamic function tests indicated IAD. After commencement of corticosteroid replacement therapy, his symptoms resolved without complications. CONCLUSIONS To our knowledge, this is the first report of a hemodialysis patient with both IAD and primary hypothyroidism. This case highlights the importance of regular assessments of thyroid function for primary hypothyroidism in hemodialysis patients, even when they are asymptomatic. Furthermore, timely dynamic endocrine testing of hypothalamic-pituitary-adrenal function is needed to diagnose possible IAD in hemodialysis patients with symptoms suggestive of adrenal insufficiency, even in the absence of abnormal laboratory findings such as electrolyte imbalances or low morning blood levels of cortisol or adrenocorticotropic hormone.

Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer.

A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.

Isolated Adrenocorticotropic Hormone Deficiency Presenting with Severe Hyponatremia and Rhabdomyolysis: A Case Report and Literature Review.

BACKGROUND Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder characterized by central adrenal insufficiency (AI) but normal secretion of pituitary hormones other than adrenocorticotropic hormone. IAD usually presents with unspecific symptoms of AI, such as anorexia and fatigue, but some patients present with a variety of atypical manifestations. Rhabdomyolysis is a potentially life-threatening clinical syndrome caused by skeletal muscle injury with the release of muscle cell contents into the circulation. A wide variety of disorders can cause rhabdomyolysis. Herein, we report an unusual case of IAD presenting with hyponatremia and rhabdomyolysis. CASE REPORT A 67-year-old Japanese woman with a 2-month history of anorexia and fatigue was diagnosed with severe hyponatremia (serum sodium, 118 mEq/L) and rhabdomyolysis (serum creatine phosphokinase, 6968 IU/L), after 2 days of vomiting and muscle weakness. Physical and laboratory findings did not show dehydration or peripheral edema. Her rhabdomyolysis resolved with normalization of serum sodium levels during administration of sodium chloride. However, her anorexia and fatigue remained unresolved. After reducing the amount of sodium chloride administered, the patient still had hyponatremia. Detailed endocrinological examinations indicated IAD; her hyponatremia was associated with inappropriately high plasma arginine vasopressin levels. The patient received corticosteroid replacement therapy, which resolved her anorexia, fatigue, excessive arginine vasopressin, and hyponatremia. CONCLUSIONS This case highlights the importance of considering the possibility of central AI in patients with hyponatremia and excessive arginine vasopressin levels. In addition, rhabdomyolysis associated with hyponatremia can be an important manifestation of IAD.

Isolated adrenocorticotropic hormone deficiency and thyroiditis associated with nivolumab therapy in a patient with advanced lung adenocarcinoma: a case report and review of the literature.

INTRODUCTION: Immune checkpoint inhibitors are a promising class of anticancer drugs. The clinical benefits afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events that affect multiple organs, and endocrine immune-related adverse events include thyroiditis and hypophysitis. Hypophysitis is less frequent and has a less severe clinical presentation in patients treated with other immune checkpoint inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, than in those treated with ipilimumab. However, studies have described isolated adrenocorticotropic hormone deficiency cases associated with nivolumab, pembrolizumab, and atezolizumab therapy, most of which occurred during the course of immune checkpoint inhibitor therapy. We report a rare case of patient with isolated adrenocorticotropic hormone deficiency that occurred after nivolumab therapy. CASE PRESENTATION: A 69-year-old Japanese woman with advanced lung adenocarcinoma developed painless thyroiditis with transient elevations of serum thyroid hormones during 3 months of cancer treatment with nivolumab and began thyroid hormone replacement therapy for subsequent primary hypothyroidism. Four months after nivolumab therapy was discontinued, she developed isolated adrenocorticotropic hormone deficiency; corticosteroid replacement therapy relieved her secondary adrenal insufficiency symptoms, such as anorexia and fatigue. Human leukocyte antigen typing revealed the presence of DRB1*04:05-DQB1*04:01-DQA1*03:03 and DRB1*09:01-DQB1*03:03-DQA1*03:02 haplotypes, which increase susceptibility to autoimmune polyendocrine syndrome associated with thyroid and pituitary disorders in the Japanese population. CONCLUSIONS: Our patient developed thyroiditis during cancer treatment with nivolumab and subsequently exhibited isolated adrenocorticotropic hormone deficiency 4 months after discontinuing the drug. Administration of nivolumab in combination with a genetic predisposition to polyglandular autoimmunity probably caused both the thyroiditis and hypophysitis, resulting in primary hypothyroidism and isolated adrenocorticotropic hormone deficiency, respectively, in our patient. The present case highlights the need for physicians to be aware that endocrine immune-related adverse events, including hypophysitis, can occur more than several months after discontinuing a drug.

A case of normotensive incidentally discovered adrenal pheochromocytoma.

Pheochromocytomas are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. The clinical presentation includes headache, palpitation, and hypertension, but pheochromocytomas are sometimes clinically silent. The present case highlights the importance of biochemical testing for pheochromocytoma in patients with adrenal incidentaloma, even if they are completely normotensive and asymptomatic.

Reversible Non-parkinsonian Bradykinesia with Impaired Frontal Lobe Function as the Predominant Manifestation of Adrenal Insufficiency.

A 69-year-old Japanese man with a history of suprasellar surgery and irradiation developed bradykinesia and mild fatigue without muscle weakness, myalgia, pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An endocrinological work-up revealed anterior hypopituitarism associated with secondary adrenal insufficiency. Higher brain function tests indicated an impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal lobe dysfunction improved within 2 weeks after the initiation of corticosteroid replacement therapy. To our knowledge, this is the first reported case of adrenal insufficiency manifesting as non-parkinsonian bradykinesia. Physicians should consider reversible non-parkinsonian bradykinesia associated with frontal lobe dysfunction as an unusual manifestation of adrenal insufficiency.

Glutamic Acid Decarboxylase Autoantibody-negative Slowly Progressive Type 1 Diabetes Mellitus: A Case Report and Literature Review.

A 59-year-old non-obese Japanese woman developed diabetes mellitus with a negative glutamic acid decarboxylase autoantibody (GADA) test result. Her hyperglycemia was initially well controlled by oral hypoglycemic agents; however, despite continued treatment the hyperglycemia gradually worsened. As she had endogenous insulin deficiency and tested positive for insulin autoantibody (IAA), insulin therapy was initiated. Few studies have investigated GADA-negative patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA-positive SPT1D patient progressed from the clinical onset of diabetes mellitus to starting insulin therapy relatively quickly (1.5 years), similarly to other previously reported non-obese patients with GADA-positive SPT1D.

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13-1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08-1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

Isolated Adrenocorticotropin Deficiency due to Nivolumab-induced Hypophysitis in a Patient with Advanced Lung Adenocarcinoma: A Case Report and Literature Review.

A 63-year-old Japanese woman with advanced lung adenocarcinoma developed isolated adrenocorticotropin deficiency caused by immune checkpoint inhibitor (ICI)-related hypophysitis following 8 months of nivolumab therapy. Prompt corticosteroid replacement therapy effectively relieved her secondary adrenal insufficiency symptoms and allowed her to pursue nivolumab therapy, which had been effective for the control of lung adenocarcinoma. Human leukocyte antigen (HLA) typing revealed the presence of the DRB1*04:05-DQA1*03:03-DQB1*04:01 haplotype, which is associated with susceptibility to autoimmune polyglandular syndrome with pituitary disorder in the Japanese population. This case suggests that genetic factors, such as HLA, contribute to the development of endocrinopathies induced by ICIs.

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

BACKGROUND: Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. CASE PRESENTATION: An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. CONCLUSIONS: Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

Generalized Status Epilepticus in a Patient with Acute-onset Type 1 Diabetes Mellitus Associated with Severe Kidney Dysfunction: A Case Report and Literature Review.

A 65-year-old Japanese man with advanced chronic kidney disease (CKD) developed acute-onset type 1 diabetes mellitus (T1D) that was associated with severe acute kidney injury and was manifested by generalized tonic-clonic status epilepticus. His seizures resolved without recurrence after correcting the diabetic ketoacidosis. Although hyperglycemia is an important cause of acute symptomatic seizure (ASS), patients with ketotic hyperglycemia develop ASS less frequently. In this T1D case with CKD, severe hyperglycemia in conjunction with other metabolic insults, such as uremia, hyponatremia, and hypocalcemia, probably provoked his seizure despite the severe ketonemia.

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

BACKGROUND: Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. CASE PRESENTATION: A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. CONCLUSIONS: The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.