With the generalized use of highly sensitive thyroid stimulating hormone (TSH) and free thyroid hormone assays, most thyroid function tests (TFTs) are straightforward to interpret and confirm the clinical impressions of thyroid diseases. However, in some patients, TFT results can be perplexing because the clinical picture is not compatible with the tests or because TSH and free T4 are discordant with each other. Optimizing the interpretation of TFTs requires a complete knowledge of thyroid hormone homeostasis, an understanding of the range of tests available to the clinician, and the ability to interpret biochemical abnormalities in the context of the patient's clinical thyroid status. The common etiologic factors causing puzzling TFT results include intercurrent illness (sick euthyroid syndrome), drugs, alteration in normal physiology (pregnancy), hypothalamic-pituitary diseases, rare genetic disorders, and assay interference. Sick euthyroid syndrome is the most common cause of TFT abnormalities encountered in the hospital. In hypothalamic-pituitary diseases, TSH levels are unreliable. Therefore, it is not uncommon to see marginally high TSH levels in central hypothyroidism. Drugs may be the culprit of TFT abnormalities through various mechanisms. Patients with inappropriate TSH levels need a differential diagnosis between TSH-secreting pituitary adenoma and resistance to thyroid hormone. Sellar magnetic resonance imaging, serum α-subunit levels, serum sex hormone-binding globulin levels, a thyrotropin-releasing hormone stimulation test, trial of somatostatin analogues, and TR-β sequencing are helpful for the diagnosis, but it may be challenging. TFTs should be interpreted based on the clinical context of the patient, not just the numbers and reference ranges of the tests, to avoid various pitfalls of TFTs and unnecessary costly evaluations and therapies.
Diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; Euthyroid Sick Syndromes ; Homeostasis ; Humans ; Hyperthyroidism ; Hypothyroidism ; Magnetic Resonance Imaging ; Physiology ; Pituitary Neoplasms ; Rare Diseases ; Reference Values ; Sex Hormone-Binding Globulin ; Somatostatin ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyrotropin-Releasing Hormone

Sheehan's syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. The onset in most cases is several months or even years after the inciting delivery, so it is often unrecognized and not adequately treated. Because SS often evolves slowly, it is usually diagnosed late. We report a 47-year old woman with loss of consciousness. Fourteen years ago, she had postpartum hemorrhage with subsequent amenorrhea and failure to lactate. Laboratory investigation showed low blood sugar and serum sodium levels, amid normal cortisol and thyroid function tests. Magnetic resonance imaging (MRI) of the pituitary revealed an empty sella consistent with SS. The presentation of hypoglycemia and hyponatremia are less known complications of Sheehan's syndrome with only a few documented in case reports.

Human ; Female ; Middle Aged ; Amenorrhea ; Empty Sella Syndrome ; Hydrocortisone ; Hypoglycemia ; Hyponatremia ; Hypopituitarism ; Lactic Acid ; Magnetic Resonance Imaging ; Pituitary Diseases ; Pituitary Gland ; Postpartum Hemorrhage ; Thyroid Function Tests ; Unconsciousness ; Growth Hormone ; Hormones

PURPOSE: Short stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature. METHODS: We retrospectively reviewed the medical records of 3,371 patients who visited Severance Children's Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed. RESULTS: Approximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%). CONCLUSION: A majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.
Ambulatory Care Facilities ; Child* ; Growth Hormone ; Humans ; Insulin-Like Growth Factor I ; Medical Records ; Pituitary Function Tests ; Retrospective Studies

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above. METHODS: A 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1. RESULTS: Genomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion. CONCLUSION: There is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected.
Aged ; Brain ; Cavernous Sinus ; Cranial Nerve Diseases ; Diagnosis ; Diagnostic Errors* ; Diplopia ; Exons ; Female ; Genetic Testing ; Hemangioma, Cavernous* ; Humans ; Islets of Langerhans ; Leukocytes ; Magnetic Resonance Imaging ; Multiple Endocrine Neoplasia Type 1* ; Neurologic Manifestations ; Paralysis ; Pituitary Function Tests ; Pituitary Neoplasms ; Prevalence

Functional defects of the pituitary gland are a rare cause of pubertal delay. The pituitary stalk is an important structure that connects the hypothalamus and pituitary gland. A defect in fusion of the pituitary stalk and anterior pituitary gland will block the function of the anterior pituitary gland. A 28-year-old man was referred to our clinic with poorly developed secondary sexual characteristics. He had undeveloped facial, axillary, and pubic hair and was Tanner stage I. Laboratory tests gave random serum testosterone < 0.025 ng/mL, luteinizing hormone (LH) < 0.1 mIU/mL, follicle-stimulating hormone (FSH) 0.626 mIU/mL, thyroid-stimulating hormone (TSH) 6.85 microIU/mL, and fT4 6.96 pmol/L. Sella magnetic resonance imaging (MRI) showed no pituitary stalk enhancement. The response in the combined pituitary function test revealed multiple hormonal defects, while the TSH response to thyrotropin-releasing hormone (TRH) was exaggerated and delayed. Therefore, we concluded that pituitary stalk dysgenesis had led to hypothalamic-type panhypopituitarism.
Adult ; Follicle Stimulating Hormone ; Hair ; Humans ; Hypopituitarism ; Hypothalamus ; Luteinizing Hormone ; Magnetic Resonance Imaging ; Pituitary Function Tests ; Pituitary Gland ; Pituitary Gland, Anterior ; Puberty, Delayed ; Testosterone ; Thyrotropin ; Thyrotropin-Releasing Hormone

Adrenal insufficiency is caused by either primary adrenal failure or by hypothalamic-pituitary impairment of the corticotropic axis which is predominantly due to long-term glucocorticoid treatment or by pituitary disease. Primary adrenal failure is a rare disease that is life-threatening when overlooked whle adrenal failure secondary to hypothalamo-pituitary disease is a common clinical problem that has serious impact on the quality of life. Recent data suggests that the health-related quality of life in many patients with adrenal insufficiency is more severely impaired than previously thought and that current hormone replacement strategies are insufficient to prevent increased morbidity and mortality due to the disease. Therefore, the optimization and careful monitoring of glucocorticoid and mineralocorticoid replacement therapy remains one of the most challenging tasks in endocrinology. Leaving treatment aside, diagnosis of adrenal insufficiency is also challenging, because the main presenting symptoms such as fatigue, anorexia, and weight loss are non-specifically associated with many other common ailments, delaying a correct diagnosis. Some pitfalls in diagnostic work-up, particularly in the identification of secondary adrenal insufficiency, make the diagnosis even more difficult. Despite the difficulties, the complications associated with adrenal insufficiency make the rapid diagnosis and proper management of adrenal failure are important tasks for all physicians. We review here current standards for clinical assessment, diagnosis and treatment of adrenal insufficiency in light of recent research findings.
Addison Disease ; Adrenal Cortex Function Tests ; Adrenal Insufficiency ; Anorexia ; Endocrinology ; Fatigue ; Glucocorticoids ; Humans ; Light ; Pituitary Diseases ; Quality of Life ; Rare Diseases ; Weight Loss ; Axis, Cervical Vertebra

Granulomatous hypophysitis is a rare pituitary condition that commonly presents with enlargement of the pituitary gland. A 31-year-old woman was admitted to the hospital with a severe headache and bitemporal hemianopsia. Magnetic resonance imaging (MRI) showed an 18 x 10-mm sellar mass with suprasellar extension and compression of the optic chiasm. Interestingly, brain MRI had shown no abnormal finding 4 months previously. On hormonal examination, hypopituitarism with mild hyperprolactinemia was noted. The biopsy revealed granulomatous changes with multinucleated giant cells. We herein report this rare case and discuss the relevant literature.
Adult ; Biopsy ; Female ; Giant Cells/pathology ; Granuloma/complications/*diagnosis/therapy ; Headache/etiology ; Hemianopsia/etiology ; Humans ; Hyperprolactinemia/etiology ; Hypopituitarism/etiology ; Inflammation/complications/*diagnosis/therapy ; Magnetic Resonance Imaging ; Optic Chiasm/pathology ; Pituitary Diseases/complications/*diagnosis/therapy ; Pituitary Function Tests ; Pituitary Gland/*pathology/surgery ; Predictive Value of Tests ; Severity of Illness Index ; Treatment Outcome

Thyrotropin (TSH)-secreting pituitary adenoma is a very rare disease. In one-quarter of patients suffering from this disease, the pituitary tumor secretes other anterior pituitary hormones. Herein, we report a case of pituitary adenoma with simultaneous secretion of TSH and growth hormone (GH). A 34-year-old female visitied local hospital complaining of sweating, intermittent palpitation, and weight loss of 8 kg within 1 year. The patient had undergone trans-sphenoidal surgery 3 years prior for resolution of a TSH and GH co-secreting pituitary adenoma. She had been administered somatostatin analogue prior to visiting our hospital. The patient's GH levels were suppressed to below 1 ng/mL on the 75 g oral glucose tolerance test, and her basal insulin-like growth factor-I (IGF-I) level was within normal range. Thyroid function tests demonstrated increased levels of both free thyroxine and TSH. Sella-MRI revealed pituitary adenoma at the floor of the pituitary fossa, approximately 2 cm in height. Therefore, she was diagnosed with residual TSH-secreting pituitary adenoma. The patient again underwent trans-sphenoidal surgery and entered complete remission, based on hormone levels and MRI findings.
Adult ; Female ; Floors and Floorcoverings ; Glucose Tolerance Test ; Growth Hormone ; Humans ; Pituitary Hormones, Anterior ; Pituitary Neoplasms ; Rare Diseases ; Reference Values ; Somatostatin ; Stress, Psychological ; Sweat ; Sweating ; Thyroid Function Tests ; Thyrotropin ; Thyroxine ; Weight Loss

Growth hormone (GH) and thyroid stimulating hormone (TSH)-secreting pituitary adenomas are very rare and they account for only 0.5% for all pituitary adenomas. These adenomas are usually treated with surgery, but this surgery is not easy because the tumor is usually huge and invasive. We reported here on a case of a GH-TSH-secreting adenoma in a 23-year-old male patient who was initially treated with octreotide LAR. He presented with symptoms of headache, palpitation and a visual defect that he had for the 3 months. He had hypertrophy of the frontal bone and enlargement of both the hands and feet. The visual field test showed bitemporal hemianopsia. The laboratory examinations showed high serum levels of free T4, TSH and free alpha-subunit. Additionally, the serum levels of GH and insulin-like growth factor-I (IGF-I) were increased. GH was not suppressed below 1microg/L by an oral 75g glucose loading test, and TSH was not stimulated by thyrotropin-releasing hormone (TRH). Because sellar MRI showed invasive macroadenoma encasing the vessels, we initially tried octreotide LAR for treatment. A year later, the IGF-I and thyroid function tests were normalized and the size of the tumor was reduced with cystic change. The symptoms of palpitation and headache were improved without a change of the visual field defect.
Acromegaly ; Adenoma ; Foot ; Frontal Bone ; Glucose ; Growth Hormone ; Hand ; Headache ; Hemianopsia ; Humans ; Hypertrophy ; Insulin-Like Growth Factor I ; Male ; Octreotide ; Pituitary Neoplasms ; Thyroid Function Tests ; Thyrotropin ; Thyrotropin-Releasing Hormone ; Visual Field Tests ; Visual Fields ; Young Adult

A 39-year-old woman presented with a 20 day history of recurrent hypoosmolar hyponatremia. Because her volume status seemed to be normal, the most suspected causes of her hyponatremia were adrenal insufficiency and hypothyroidism. Endocrinologic examination, including a combined pituitary function test, showed TSH and ACTH deficiency without GH deficiency, and hyperprolactinemia was also present. Sella MRI showed a pituitary mass, stalk thickening and loss of the normal neurohypophysial hyperintense signal on the T1 weighted image. Pathologic exam demonstrated granulomatous lesions and Langhans' multinucleated giant cells with inflammatory cell infiltration. After high dose methylprednisolone pulse therapy (1 g/day for 3 days) with subsequent prednisolone and levothyoxine replacement, there was no more recurrence of the hyponatremia. The sella MRI on the 6th month showed decreased mass size, narrowed stalk thickening and the reappearance of the normal neurohyphophysial hyperintense signal. She is currently in a good general condition and is receiving hormone replacement therapy.
Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Adult ; Female ; Giant Cells ; Hormone Replacement Therapy ; Humans ; Hyperprolactinemia ; Hyponatremia ; Hypothyroidism ; Methylprednisolone ; Pituitary Function Tests ; Prednisolone ; Recurrence