OBJECTIVE: The simultaneous occurrence of primary ovarian insufficiency (POI) and autoimmune diseases has been noted and debated in some epidemiological research. This bidirectional two-sample Mendelian randomization (MR) study aimed to investigate the causal relationships between autoimmune diseases and POI.
METHODS: We obtained summary-level data for ten autoimmune diseases and POI from published large-scale genome-wide association studies and the FinnGen consortium of European ancestry. A series of filtering steps was performed to discern independent genetic variants. Causal estimates were mainly calculated by the inverse variance weighting method and verified through multiple sensitivity analyses.
RESULTS: Of the ten autoimmune diseases, genetically predicted Addison\'s disease (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.09-1.47, P = 0.003) and systemic lupus erythematosus (OR = 1.12, 95% CI 1.02-1.24, P = 0.021) were associated with an increased risk of POI, and sensitivity analyses confirmed the robustness of the results. In addition, there were weak associations between liability to POI and elevated risks of type 1 diabetes (OR = 1.05, 95% CI 1.00-1.10, P = 0.046) and autoimmune thyroid disease (OR = 1.03, 95% CI 1.01-1.05, P = 0.015).
CONCLUSIONS: This study revealed that Addison\'s disease and systemic lupus erythematosus are potential risk factors for POI, underscoring the necessity to consider the impact of autoimmune factors in the diagnosis and treatment of POI.

Addison\'s disease which is due to dysfunction of the adrenal gland, with abnormal secretion of glucocorticoids and mineralocorticoids, is rare. By inducing inflammation and disorders of water and electrolyte metabolism, Addison\'s disease may accelerate progression of co-existed cardiovascular diseases. Addison\'s disease combined with cardiovascular disease is infrequent, only 10 cases in the literature.
We reported a 51-year-old male patient with unstable angina pectoris and hypotension. Changes on coronary angiography within 2 years suggested rapid progression of coronary artery disease in a patient with low cardiovascular risk. An additional clue of skin hyperpigmentation, fatigue and further examination confirmed the diagnosis of Addison\'s disease caused by adrenal tuberculosis. After hormone replacement treatment, the frequency and severity of the angina pectoris were alleviated significantly, as were hypotension, hyperpigmentation and fatigue.
The combination of Addison\'s disease and coronary artery disease in one patient is rare. Addison\'s disease can induce inflammation and disorders of water and electrolyte metabolism, which may further accelerate the course of coronary artery disease. Meanwhile, the hypotension in Addison\'s disease may affect the coronary blood flow, which may result in an increased susceptibility to unstable angina in the presence of coronary stenosis. So, we should analyze comprehensively if the coronary artery disease progress rapidly.

We report the case of a 47-year-old male patient with pigmentation of the head, face and hands, who was initially diagnosed as having primary adrenal insufficiency (Addison\'s disease). Laboratory testing, imaging and physical examination revealed subclinical hypothyroidism, high circulating prolactin and oestradiol concentrations, gynaecomastia, lymphadenopathy, splenomegaly and weakness of both lower limbs. These findings led us to consider whether a single or multiple diseases were present in this patient. Indeed, Addison\'s disease can represent one aspect of a wider systemic disease. Therefore, we performed further examinations, and found high serum M protein (5.1%) and vascular endothelial growth factor [1005.30 pg/mL (normal range 0 to 142 pg/mL)] concentrations. As a consequence, we diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. Consequently, when a single disease cannot fully explain the multiple symptoms and signs of one patient, clinicians should consider the possibility of the presence of a wider syndrome and undertake more detailed diagnostic testing.

Thymoma is the most common paraneoplastic syndrome-associated tumor. It is related to a variety of autoimmune diseases including myasthenia gravis, systemic lupus erythematosus, and hypogammaglobulinemia. Only a few reports of thymoma associated with Addison\'s disease have been reported to date. Herein, we report a novel case of thymoma complicated with autoimmune Addison\'s disease and interstitial lung disease. The patient developed adrenal crisis with persistent hypotensive shock and heart block after needle biopsy. Acute exacerbation of the interstitial lung disease was also observed, accompanied by severe respiratory failure. After treatment with glucocorticoids, somatostatin, and temporary pacemaker implantation, the patient\'s condition improved, and the thymoma had shrunk in size. Finally, he underwent transsternal extended thymectomy and lymph node dissection. Hydrocortisone was given intravenously before surgery, on the operation day and after the surgery. The operation was uneventful, and no hypotension or fever occurred. Cortisol and ACTH were still obviously abnormal at 1 month post-surgery. The clinical manifestations of Addison\'s disease and interstitial lung disease are hidden and can be easily overlooked. However, in the postoperative period, Addison\'s disease can lead to adrenal crisis developing, which can progress to life-threatening shock, arrhythmia, and acute respiratory failure. Therefore, clinicians should be aware of this phenomenon and consider a regimen combining proactive glucocorticoid replacement therapy with somatostatin to preserve the life of such patients.

BACKGROUND: Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission, and it is typified by fluctuating degrees and variable combinations of weakness in the ocular, bulbar, limb, and respiratory muscles. Under rare circumstances, MG can be accompanied by Addison\'s disease.
METHODS: Here, we reported the case of a 57-year-old Chinese woman with MG. She experienced progressive muscle weakness for 1 week. MG with acute exacerbation was initially suspected. However, further biochemistry tests found mild hyperkalemia (5.6 mEq/L) and a lower renal potassium excretion rate. Consequently, low aldosterone action was highly suspected. Further findings included a suppressed cortisol level, a higher adrenocorticotropic hormone concentration, and 21-hydroxylase antibody positivity, supporting a diagnosis of primary adrenal insufficiency due to autoimmune adrenalitis.
CONCLUSIONS: We successfully demonstrated that adrenal insufficiency could be diagnosed, due to the presence of hyperkalemia. This case suggested a need for clinicians to consider the possible coincidence of adrenal insufficiency in a patient with MG and hyperkalemia. Early hormone supplementation should be begun.

UNASSIGNED: 21-hydroxylase deficiency (21 OHD) is the most common form of congenital adrenal hyperplasia (CAH) and it has been widely described in the literature. Adrenocortical incidentalomas are unfrequently the presenting manifestations of CAH, especially in nonclassical form of 21 OHD (NC 21 OHD). Myelolipoma has previously been reported more frequently than other adrenal adenomas associated with CAH.
UNASSIGNED: We report a 40-year old male case of NC 21 OHD with hypoadrenocorticism after unilateral adrenalectomy of the right side because of a large solid incidentaloma (5×4×4cm3) at the age of 31. This patient began to suffer from obvious symptoms of adrenal insufficiency after 9 years from the surgery. He was reviewed and a very low-density adrenal mass (4.1×3.9cm) was found on computed tomography of the abdomen. After he was admitted to our hospital, this patient was confirmed with NC 21 OHD and presented low level cortisol, striking elevated ACTH, aldosterone insufficiency, increased 17-hydroxyprogesterone, progesterone, decreasing androgens and azoospermatism.
UNASSIGNED: Patients with 21 OHD could be on risk not only for adrenal hyperplasia, but also to develop adrenal adenomas, particularly if the disease was poorly controlled.

Background Primary adrenal insufficiency (PAI) in children is a rare condition and potentially lethal. The clinical characteristics are non-specific. It may be manifested as a chronic condition or crisis. The etiologies of PAI in children are different from the adult population. Therefore, diagnostic investigation becomes challenging. Methods A retrospective study was conducted at The First Affiliated Sun Yat Sen University Pediatric Endocrine unit between September 1989 and July 2016. Results A total of 434 patients (237 males, 197 females) were identified as having PAI. Congenital adrenal hyperplasia (CAH) was the most frequent etiology (83.4%, n = 362, male:female = 174:188), of which 351 (97.2%) were 21-hydroxylase deficiency (21-OH) CAH. Non-CAH etiology accounted for 11.3% (n = 49, male:female = 47:2), of which 46 (93.9%) were of non-autoimmune. The etiologies of the 49 cases were adrenoleukodystrophy (ALD; n = 22), X-linked adrenal hypoplasia congenital (X-AHC; n = 20), autoimmune polyglandular syndrome (APS; n = 3), triple A syndrome (n = 2), steroidogenic factor 1 (SF-1) gene mutation (n = 1) and adrenalectomy (n = 1). The etiology was not identified for 23 patients (5.3%, male:female =16:7). Clinical symptoms were in accordance with the incidence of genital ambiguity (42.6%), digestive symptoms (vomiting and diarrhea) (35.5%), failure to thrive (26.5%), gonadal-associated symptom (premature puberty, sexual infantilism and amenorrhea) (21.2%), hyperpigmentation (9.7%), adrenal crisis (AC; 4.1%), neurological symptoms (3.2%), fatigue (2.5%) and prolonged jaundice (2.1%). Through physical examination, 58.5% were found to have hyperpigmentation. Conclusions This study spanned 29 years at our institution. The etiology of PAI in children was mostly of congenital forms, which exhibits a wide spectrum of clinical characteristics. For etiological diagnosis, chromosomal karyotyping is recommended for female phenotype patients.