Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: A 55-year-old woman presented with ill-defined right abdominal pain and, on evaluation, was diagnosed to have a large right adrenal mass (9.5×8.5×8.7 cm). Although normotensive, she had markedly increased plasma free normetanephrine (8,500 ng/L (normal range: 20.10-135.40)). Pre-operatively, she received alpha-adrenergic receptor blockade (prazosin) followed by beta-adrenergic receptor blockade before undergoing right laparoscopic adrenalectomy. She had an uneventful intra- and post-operative period. The microscopic section of the tumour showed a 'zellballen' pattern, with nests separated by thin fibrovascular septae, consistent with pheochromocytoma. With the increasing accessibility of imaging technologies, asymptomatic pheochromocytoma detections are increasing. The absence of hypertension or metabolic features can be found in 30% of the cases of pheochromocytoma. Small tumour size, dopamine secretion, extensive necrosis, absence of neuropeptide Y, and adrenoreceptor desensitisation are possible explanations for normotensive status. Our case underscores the importance of ruling out pheochromocytoma in all adrenal incidentalomas, even in normotensive status.

Learning points: With the increasing availability of imaging techniques, pheochromocytomas are increasingly detected as incidentalomas. Pheochromocytomas can be normotensive even with significantly higher catecholamine levels and large size. Secondary diabetes mellitus can be seen in up to 50% of cases of pheochromocytomas and paraganglioma, which generally resolves after successful biochemical remission. Adequate α-blockade is preferable to prevent intra-operative haemodynamic instabilities in normotensive pheochromocytomas.

Summary: This is a case of a patient with a 10-year history of Cushing's disease (CD) that was previously treated with transsphenoidal pituitary tumour resection. Conception occurred spontaneously, and during early pregnancy recurrent CD became apparent both clinically and biochemically. Repeat transsphenoidal surgery took place during the second trimester, and the high-risk pregnancy resulted in a live neonate. Despite evidence of hypercortisolism and recurrent CD at 6 months postpartum, the patient had a second successful, uncomplicated pregnancy, further adding to the rarity and complexity of this case. Pregnancy in CD is rare because hypercortisolism seen in CD suppresses gonadotropin release, leading to menstrual irregularities and infertility. Diagnosis of CD is particularly challenging because many clinical and biochemical features of normal pregnancy overlap considerably with those seen in CD. Diagnosis and treatment are extremely important to reduce rates of perinatal morbidity and mortality.

Learning points: Hypercortisolism suppresses gonadotropin release, leading to menstrual irregularities and infertility. In CD, hypersecretion of both androgens and cortisol further contributes to higher rates of amenorrhoea and infertility. Pregnancy itself is a state of hypercortisolism, with very few studies detailing normal ranges of cortisol in each trimester of pregnancy for midnight salivary cortisol and urinary free cortisol testing. Treatment of CD reduces maternal morbidity and rates of foetal loss, and can be either surgical (preferred) or medical. CD can relapse, often many years after initial surgery. There are a limited number of cases of Cushing's syndrome in pregnancy, therefore, the best possible treatment is difficult to determine and should be individualised to the patient.

Summary: Hypothyroidism, affecting approximately 5% of the population, often remains undiagnosed, more so in developing countries. We report a 12-year-old girl with longstanding, untreated hypothyroidism who initially presented with proteinuria. History revealed recurrent vomiting, poor appetite, lethargy, and neurodevelopmental delays. Examination showed short stature, ptosis, outer eyebrow hair loss, myxedematous facies, dry skin, and hypertrophied calves. Investigations confirmed severe primary hypothyroidism, Hashimoto's thyroiditis, which most commonly presents between the ages of 45 and 55 years, with elevated thyroid autoantibodies and an atrophic thyroid gland. Additional findings were dyslipidemia and moderate proteinuria, both of which resolved with levothyroxine, which also improved growth. However, weight fluctuations persisted due to treatment non-adherence from financial challenges. This case illustrates a broad and atypical spectrum of complications arising from longstanding, untreated primary hypothyroidism. Awareness of such varied clinical manifestations is essential for timely diagnosis and appropriate management.

Learning points: Undiagnosed cases of hypothyroidism are more prevalent in poor-resource setups. Longstanding hypothyroidism can lead to varied presentations involving different organs, including the kidneys and gastrointestinal system, besides its profound negative effect on growth and brain development. Dyslipidemia and ptosis have been reported as well. Calf muscle hypertrophy, Kocher-Debré-Semelaigne syndrome, has been reported in longstanding hypothyroidism.

Summary: Several reports focus on azole-induced primary adrenal insufficiency (PAI); however, none have specifically focused on the absence of hypotension and hyperkalemia among the clinical features of adrenal insufficiency (AI). Here, we report a case of posaconazole-induced PAI with normal blood pressure. A 74-year-old male patient was diagnosed with lymphoma in July 2019 and underwent chemotherapy. He gradually began to experience anorexia, fatigue, and a fever of 37°C-38°C from mid-March 2022. He was diagnosed with pneumonia on April 4, 2022, and antibiotics and posaconazole at 300 mg daily were initiated post-hospitalization. Symptoms of anorexia, nausea, fatigue, and fever demonstrated no improvement despite the regression of the consolidation on the chest computed tomography. The early morning cortisol level was 2.4 μg/dL despite a high adrenocorticotropic hormone (ACTH) level (101.7 pg/mL). Therefore, we diagnosed the patient with PAI according to the low cortisol level (maximum of 8.6 μg/dL at 60 min) in a rapid ACTH stimulation test. Despite having PAI, the patient exhibited normal blood pressure and hypokalemia. Posaconazole was considered to cause PAI; therefore, it was discontinued, and hydrocortisone replacement was initiated. His symptoms improved, and rapid ACTH stimulation test reassessment 1 month after posaconazole discontinuation revealed normal basal ACTH, cortisol, and ACTH response. However, the renin-angiotensin-aldosterone system did not fully improve, as opposed to the hypothalamic-pituitary-adrenal axis. Posaconazole inhibits 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase type 2, causing pseudohyperaldosteronism, which persists. Notably, posaconazole causes PAI without hypotension and hyperkalemia, which are its major clinical characteristics.

Learning points: Posaconazole causes PAI within 1 month of initial administration. Posaconazole-induced PAI may not present with hypotension or hyperkalemia. The hypothalamic-pituitary-adrenal axis improves, but the renin-angiotensin-aldosterone system may take longer to recover, as changes persist even 1 month after posaconazole discontinuation. Hypokalemia treatment should continue carefully until pseudohyperaldosteronism resolution.

Summary: Thyroid stimulating hormone (TSH)-secreting PitNETs, also called TSHomas, are rare benign pituitary tumors with an incidence of 1.0 per million population. They are generally diagnosed in the context of central hyperthyroidism and/or mass-effect central symptomatology (e.g. headache, bitemporal hemianopsia, and panhypopituitarism). Although TSHomas are more often macroadenomas than microadenomas at the time of diagnosis, diagnosing TSHomas may be challenging because laboratory findings and clinical presentation are not always obvious. The treatment of choice is the surgical resection of the adenoma.

Learning points: TSHomas are mostly diagnosed as macroadenomas in the context of central hyperthyroidism and/or mass-effect central symptomatology. The classical pattern of central hyperthyroidism consists of elevated free thyroid hormones and inadequately normal or slightly increased TSH. If a TSHoma is suspected, the differential diagnosis of thyroid hormone resistance (RTH) must be excluded. Surgical resection is the first-line choice of therapy for TSHomas. In cases of non-operable lesions or postoperative residual tumors, pituitary fractionated stereotactic radiotherapy, radiosurgery, and/or medical treatment with somatostatin analogs can be considered as alternatives. The management of TSHomas must happen in an interdisciplinary way.

Summary: The diagnosis and management of Cushing's disease (CD) during pregnancy are challenging. Only a few cases of mixed pituitary adenomas secreting prolactin and ACTH have been reported, and none during pregnancy. We report the case of a 30-year-old woman who presented with galactorrhea, weight gain, hypertension, prediabetes, dorsal fat pad, and abdominal striae. Initial biochemical investigations revealed hyperprolactinemia with increased ACTH but no biochemical signs of hypercortisolism. Pituitary MRI showed a 10 mm pituitary adenoma, which was first considered a prolactinoma potentially co-secreting ACTH. Surgery was indicated, but the patient did not undergo treatment immediately due to lack of health insurance. Cabergoline monotherapy was initiated, with close follow-up advised until regularization of social status in Belgium. The patient was then lost to follow-up and presented 15 months later because of an early pregnancy with treatment-resistant hypertension. Biochemical evaluation during the first trimester led to the suspicion of ACTH-dependent cortisol excess and showed hyperprolactinemia despite ongoing cabergoline treatment. She underwent transsphenoidal surgery at 16 weeks of pregnancy, and pathological examination showed a single adenoma with two different cell components staining for PRL/PIT1 and ACTH/TPIT, respectively. Surgery was successful, the patient developed corticotrope insufficiency, and was able to stop antihypertensive drugs. Because of failed induction of labor (for gestational insulin-requiring diabetes), she underwent cesarean section at 39 weeks of pregnancy and gave birth to a healthy boy with no maternal or neonatal complications. Adrenal insufficiency recovered 12 months after surgery. Genetic testing for MEN1 and AIP was negative.

Learning points: Mixed ACTH- and PRL-secreting pituitary adenomas, although extremely rare, do occur and may lead to both Cushing's syndrome and galactorrhea/oligo- or amenorrhea syndrome. Cabergoline therapy is an option in such cases and may decrease both PRL and ACTH levels; however, its efficacy in controlling Cushing's disease is limited. Preconception counseling is essential in women of childbearing age suffering from secreting pituitary tumors. Management of prolactinoma during pregnancy usually includes cessation of dopamine agonists and close follow-up to detect tumor growth, especially during the third trimester. Diagnosis of Cushing's syndrome during pregnancy is challenging due to the physiological activation of the hypothalamic-pituitary-adrenal axis. Cushing's syndrome may worsen during pregnancy and is associated with severe maternal and fetal complications. Early diagnosis and treatment are essential to improve fetomaternal outcomes. Transsphenoidal surgery performed during the second trimester is an effective and safe treatment for ACTH-secreting adenomas during pregnancy.

Summary: We describe two rare cases of primary bilateral macronodular adrenal hyperplasia (PBMAH) with mild autonomous cortisol secretion (MACS), incidentally discovered and further evaluated for aberrant cortisol responses to various stimuli. In both patients, morning serum cortisol levels remained elevated following 1 mg dexamethasone suppression test (DST) and 4 mg intravenous DST, while basal adrenocorticotropic hormone (ACTH) levels were suppressed. However, 24 h urinary free cortisol and nocturnal salivary cortisol levels were within normal limits. The first case involved a 69-year-old woman who exhibited significant increases in cortisol in response to luteinizing hormone-releasing hormone (LHRH; +142%), vasopressin (+66%) and metoclopramide (+98%). Treatment with the long-acting GnRH agonist leuprolide acetate led to decreased cortisol production and normalization of ACTH levels. The second case, a 54-year-old woman, showed cortisol increases following stimulation with LHRH (+58%), cosyntropin (+1,016%) and vasopressin (+46%). However, leuprolide acetate treatment did not successfully control her hypercortisolism. These cases highlight the clinical relevance of identifying aberrant cortisol responses to specific stimuli in patients with PBMAH and MACS. Such findings may inform the use of targeted medical therapies as alternatives to unilateral or bilateral adrenalectomy. In addition, a more pronounced cortisol response to LHRH compared to other stimuli may predict a favorable response to GnRH agonist therapy.

Learning points: Systematic dynamic stimulation testing to assess cortisol response to a variety of stimuli should be offered to all patients with primary bilateral adrenal hyperplasia (PBMAH) with indication for treatment. Identification of an aberrant response suggesting potential overexpression of β-adrenergic or luteinizing hormone/chorionic gonadotropin receptors (LHCGRs) may allow the use of targeted medical therapies, instead of unilateral or bilateral adrenalectomy, to control the cortisol excess in a subset of patients. In patients with MACS who have an aberrant cortisol response following LHRH stimulation, the long-acting GnRH agonist leuprolide acetate can be used to suppress endogenous LH production and improve hypercortisolism. A greater increase in cortisol secretion following LHRH stimulation and small response to the other stimuli could potentially be predictive of a better response to treatment with leuprolide acetate.

Summary: Connshing syndrome, a distinct subtype of primary aldosteronism (PA), is characterized by the co-secretion of aldosterone and cortisol from an adrenal adenoma. This condition complicates diagnosis and treatment, as cortisol co-secretion can interfere with adrenal vein sampling (AVS), the gold standard for determining lateralization in PA. We present a case of a 57-year-old woman with resistant hypertension and an adenoma in the left adrenal gland, diagnosed with PA. During the investigation, cortisol co-secretion was identified. AVS results were confounded by this co-secretion, complicating the interpretation of lateralization. Despite this, a presumptive diagnosis of unilateral aldosteronism was made, leading to the decision for adrenalectomy. Postoperative analysis confirmed the resolution of PA and normalization of aldosterone and cortisol levels. This case emphasizes the diagnostic challenges posed by cortisol co-secretion, which can distort AVS results and complicate treatment decisions. Further research is necessary to improve diagnostic accuracy and develop tailored management strategies for patients with Connshing syndrome.

Learning points: As the number of adrenal incidentalomas identified through imaging increases, more cases of Connshing syndrome are likely to be uncovered during biochemical evaluation. The co-secretion of aldosterone and cortisol from adrenal adenomas can interfere with diagnostic tests such as AVS, leading to misinterpretation of lateralization and complicating treatment decisions. It is important to explore alternative markers to cortisol, such as plasma metanephrines, to improve AVS accuracy and guide management decisions in patients with Connshing syndrome.

Summary: A 3-week-old male infant presented with poor feeding, lethargy, and weight loss. Clinical examination revealed mildly elevated tachycardia, but otherwise there were no clinical signs evident. Initial investigations revealed hypercalcaemia, which was subsequently found to be secondary to transient thyrotoxicosis. Hypercalcaemia was managed with hyperhydration along with a low-calcium infant formula, and thyrotoxicosis responded to treatment with carbimazole. Serum calcium levels gradually normalised with resolution of the neonatal thyrotoxicosis and weight gain. Subsequently, all treatment was gradually weaned over 4 months. The infant remained clinically well on follow-up with normal growth, and his laboratory investigations normalised.

Learning points: Hypercalcaemia is a recognised complication of thyrotoxicosis. Evidence in the paediatric population is limited, and this is the first reported case of hypercalcaemia noted to occur secondary to neonatal thyrotoxicosis. Signs and symptoms of both hypercalcaemia and thyrotoxicosis can be non-specific and subtle. An awareness of the condition and a high index of suspicion are required in order to make the diagnosis. While asymptomatic neonatal hypercalcaemia may be transient and self-limiting, symptomatic patients require treatment with hyperhydration. Serum calcium levels in combination with parathyroid hormone, vitamin D, and urine calcium-creatinine ratios can help narrow the differential diagnoses, but it is important that the underlying cause is carefully investigated.

Summary: Extensive research has examined the effects of growth hormone (GH) replacement therapy for patients with hypopituitarism and GH deficiency. Positive outcomes, encompassing both conventional clinical markers and improvements in quality of life (QoL), have led to its incorporation in current clinical practice guidelines. Herein, we present how routine use of the patient-reported outcome measures information system (PROMIS) as an intuitive tool portraying patient-reported outcome measures (PROMs) can help guide and follow-up therapeutic decisions and bridge the gap between clinical parameters and patient experiences. This approach is illustrated by a patient with panhypopituitarism and HIV with low antiretroviral medication adherence. Following the initiation of GH replacement therapy, PROMIS assessments documented QoL improvements that enabled full resumption of antiretroviral medication, accompanied by resolution of previously experienced adverse effects.

Learning points: GH replacement can be an important component of hormone replacement therapy in individuals with hypopituitarism and suicidal ideations. Incorporating PROMs into endocrinological care can help guide therapy decisions in patients with hypopituitarism. Clinical signs attributed to side effects of antiretroviral therapy may overlap with those of GH deficiency, and GH replacement therapy can potentially increase medication adherence.