The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

Conn’s disease is a condition in which excessive amounts of aldosterone are secreted from the adrenal glands. Because aldosterone increases the reabsorption of sodium, it leads to a very high blood pressure.

Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus.

Some patients return spontaneously to a euthyroid state within a few months, but most patients experience a phase of hypothyroidism that takes 2 to 6 months to resolve; of this group, some develop permanent hypothyroidism. About 50% of patients, however, will develop permanent hypothyroidism within 5 years of the diagnosis of postpartum thyroiditis.

High titres of anti-TPO antibodies during pregnancy have been reported to have high sensitivity and specificity for postpartum autoimmune thyroid disease.

Bicarbonate therapy is not indicated in mild and moderate forms of DKA because metabolic acidosis will correct with insulin therapy. The use of bicarbonate in severe DKA is controversial due to a lack of prospective randomized studies. It is thought that the administration of bicarbonate may actually result in peripheral hypoxemia, worsening of hypokalaemia, paradoxical central nervous system acidosis, cerebral oedema in children and young adults, and an increase in intracellular acidosis. Because severe acidosis is associated with worse clinical outcomes and can lead to impairment in sensorium and deterioration of myocardial contractility, bicarbonate therapy may be indicated if the pH is 6.9 or less.

Synacthen test interpretation:
– Basal Cortisol level should be greater than 180nmol/L
– 30min or 60min Cortisol should be greater than 420nmol/L (whatever the basal level)
– The increment should be at least 170nmol/L, apart from in severely ill patients where adrenal output is already maximal.
The patient’s results show that she has Acute Adrenal Insufficiency
The guidelines include the following recommendations for emergency treatment:
Administer hydrocortisone: Immediate bolus injection of 100 mg hydrocortisone intravenously or intramuscularly followed by continuous intravenous infusion of 200 mg hydrocortisone per 24 hours (alternatively, 50 mg hydrocortisone per intravenous or intramuscular injection every 6 h)
Rehydrate with rapid intravenous infusion of 1000 mL of isotonic saline infusion within the first hour, followed by further intravenous rehydration as required (usually 4-6 L in 24 h; monitor for fluid overload in case of renal impairment and elderly patients)
Contact an endocrinologist for urgent review of the patient, advice on further tapering of hydrocortisone, and investigation of the underlying cause of the disease, including the diagnosis of primary versus secondary adrenal insufficiency
Tapering of hydrocortisone can be started after clinical recovery guided by an endocrinologist; in patients with primary adrenal insufficiency, mineralocorticoid replacement must be initiated (starting dose 100 μg fludrocortisone once daily) as soon as the daily glucocorticoid dose is below 50 mg of hydrocortisone every 24 hours

In SIADH, there is increased secretion of the ADH hormone resulting in increased water absorption. That’s why there would be decreased serum Na, decreased osmolarity and increased urine osmolarity.

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.
Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:
Short stature
Stocky habitus
Obesity
Developmental delay
Round face
Dental hypoplasia
Brachymetacarpals
Brachymetatarsals
Soft tissue calcification/ossification
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.
The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

Primary hyperaldosteronism, also known as Conn’s Syndrome, is one of the most common causes of secondary hypertension (HTN).
The common clinical scenarios in which the possibility of primary hyperaldosteronism should be considered include the following:
– Patients with spontaneous or unprovoked hypokalaemia, especially if the patient is also hypertensive
– Patients who develop severe and/or persistent hypokalaemia in the setting of low to moderate doses of potassium-wasting diuretics
– Patients with treatment-refractory/-resistant hypertension (HTN)
Patients with severe hypokalaemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalaemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs.

Selective sodium-glucose transporter-2 (SGLT2) is expressed in the proximal renal tubules and is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen.
Empagliflozin; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion, thus increasing the risk of urinary tract infections.

RET (rearranged during transfection) is a receptor tyrosine kinase involved in the development of neural crest derived cell lineages, kidney, and male germ cells. Different human cancers, including papillary and medullary thyroid carcinomas, lung adenocarcinomas, and myeloproliferative disorders display gain-of-function mutations in RET.
In over 90% of cases, MEN2 syndromes are due to germline missense mutations of the RET gene.
Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumours, and pheochromocytoma.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
– Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
– Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney
This patient has the central type from metastases.
In patients with central DI, desmopressin is the drug of choice. It is a synthetic analogue of antidiuretic hormone (ADH). It is available in subcutaneous, IV, intranasal, and oral preparations. Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended during the initial phase of treatment.

The patient is most likely to have Medullary Thyroid Carcinoma (MTC).
Sporadic, or isolated MTC accounts for 75% of cases and inherited MTC constitutes the rest.
Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occurs.
A 24-hour urinalysis for catecholamine metabolites (e.g., vanillylmandelic acid [VMA], metanephrine) has to be done to rule out concomitant pheochromocytoma in patients with MEN type 2A or 2B, as Pheochromocytoma must be treated before MTC.

Klinefelter’s syndrome: The low follicle-stimulating hormone (FSH) and luteinising hormone (LH), together with the low testosterone, suggests a hypogonadotropic hypogonadism. We know that there is no mental retardation, and we are told that physical examination is normal and sense of smell would usually not be tested. Consequently a diagnosis of Kallman’s is suggested. We are not told of a family history of growth delay, thus this is unlikely to be constitutional delay. The thyroid-stimulating hormone (TSH) is normal, making hypothyroidism unlikely and this together with the normal prolactin make hypopituitarism most unlikely.

According to the criteria of the World Health Organization and the American Diabetes Association, impaired glucose tolerance is defined as:
two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol/l) on the 75-g oral glucose tolerance test.

Increased levels of prolactin in men can lead to erectile dysfunction, reduced facial and body hair and on rare occasion gynecomastia with galactorrhoea.

In Conn’s syndrome hypokalaemia and hypertension are present due to high levels of aldosterone with normal to high sodium levels. In this disease, the patient presents with hypertension and feelings of tiredness or fatigue.

Carcinoid tumours are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. They can be seen in other organs, including the lungs, mediastinum, thymus, liver, bile ducts, pancreas, bronchus, ovaries, prostate, and kidneys. While carcinoid tumours tend to grow slowly, they have the potential to metastasise.
Signs and symptoms seen in larger tumours may include the following:
– Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome.
– Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck.
– Diarrhoea and malabsorption (84%): Watery, frothy, or bulky stools, gastrointestinal (GI) bleed or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps.
– Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure with tachycardia and hypertension.
– Wheezing or asthma-like syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnoea.
– Pellagra with scale-like skin lesions, diarrhoea and mental disturbances.
– Carcinoid crisis can be the most serious symptom of the carcinoid tumours and life-threatening. It can occur suddenly or after stress, including chemotherapy and anaesthesia.

The external laryngeal nerve may be injured or traumatized following thyroid surgery due to its close proximity, which may result in hoarseness or loss of voice.

These symptoms represent hemiballismus which is common in diabetic patients after the infarction of contralateral subthalmic nucleus. These symptoms are usually present during activity phase and resolve while resting.

This patient has hypercalcaemia due to hyperparathyroidism. However, the intestinal absorption of calcium is mainly controlled by 1,25 dihydroxy-vitamin D. Under the influence of calcitriol (active form of vitamin D), intestinal epithelial cells increase their synthesis of calbindin (calcium-binding carrier protein) necessary for active calcium ion absorption.

The patient has primary Hypogonadism.
Since he already had two children, Klinefelter syndrome is excluded and the patient does not need karyotyping.
His lab results are normal indicating normal pituitary gland functions.
So the next step is testicular ultrasound as testicular tumour, infiltration or idiopathic failure is suspected.

Impaired glucose tolerance means that blood glucose is raised beyond normal levels, but not high enough to warrant a diabetes diagnosis. With impaired glucose tolerance you face a much greater risk of developing diabetes and cardiovascular disease. Impaired glucose tolerance is defined as 2-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in fasting patients.

People with diabetes are prone to foot problems that develop due to prolonged periods of high blood sugar levels. Diabetic neuropathy and peripheral vascular disease are the two main causes of foot problems and both can have serious complications. Diabetes can cause serious foot problems that can result in feet or limb loss, deformity, and infections. However, it is possible for a person to prevent or minimize many of these problems. While controlling blood sugar by following the recommended diabetes treatment plans is the best way to prevent these serious problems, self-care and regular check-ups with a doctor can also help prevent problems from developing.

The patient is most likely to have Postpartum thyroiditis which goes through 2 phases; hypothyroid and a hyperthyroid phase.
The hyperthyroid phase of postpartum thyroiditis occurs between 2 and 10 months postpartum. Most commonly, it presents at 3 months. Symptoms more common in women with hyperthyroid postpartum thyroiditis include palpitations, fatigue, heat intolerance, and irritability/nervousness. The frequency of asymptomatic hyperthyroidism is 33%.
Untreated, the hyperthyroidism resolves spontaneously within 2-3 months. This phase is diagnosed by the combination of a low serum TSH concentration in the presence of thyroid peroxidase antibodies, in women who are TSH receptor antibody-negative. Free T4 levels are typically elevated but may be normal.
Treatment of hyperthyroidism, when necessary, is based on symptom severity and should be a joint decision of patient and physician. Beta-blockers such as propranolol are given to alleviate palpitations, irritability, and nervousness. The morbidity associated with treatment is the side effects of beta-blockade. The downside of withholding treatment is allowing the woman to remain symptomatic. Antithyroid medicines (thioureas) are not a potential treatment alternative, because the hyperthyroidism is caused by destructive thyroiditis resulting in the release of preformed thyroid hormone.

11-beta hydroxylase is stimulated by ACTH and responsible for conversion of 11-deoxycortisol to cortisol and deoxycorticosterone to corticosterone.

In 11-beta hydroxylase deficiency, the previously mentioned conversions are partially blocked, leading to:
– Increased levels of ACTH
– Accumulation of 11-deoxycortisol (which has limited biological activity) and deoxycorticosterone (which has mineralocorticoid activity)
– Overproduction of adrenal androgens (DHEA, androstenedione, and testosterone)

Patients who have autonomously functioning nodules should be treated definitely with radioactive iodine or surgery.
Na131 I treatment – In the United States and Europe, radioactive iodine is considered the treatment of choice for Toxic Nodular Goitre. Except for pregnancy, there are no absolute contraindications to radioiodine therapy.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

Once thyrotoxicosis has been identified by laboratory values, the thyroid radio-iodine uptake and scan may be used to help distinguish the underlying aetiology. Thyroid radioiodine uptake is raised in Graves’ disease. It may be normal or raised in patients with a toxic multinodular goitre. It is very low or undetectable in thyrotoxicosis resulting from exogenous administration of thyroid hormone or the thyrotoxic phase of thyroiditis.

The patient most likely has Klinefelter’s syndrome.
Klinefelter syndrome (KS) refers to a group of chromosomal disorders in which the normal male karyotype, 46,XY, has at least one extra X chromosome. XXY aneuploidy, the most common human sex chromosome disorder. It is also the most common chromosomal disorder associated with male hypogonadism and infertility.
Klinefelter syndrome is characterized by hypogonadism (micro-orchidism, oligospermia/azoospermia), gynecomastia in late puberty, hyalinization and fibrosis of the seminiferous tubules, elevated urinary gonadotropin levels, and behavioural concerns.

The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.
DiGeorge’s syndrome (DGS) is a developmental abnormality affecting the thymus. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia).

Sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated.
Organic nitrates and nitric oxide (NO) donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO via increasing cGMP concentrations.

Treated breast malignancy is pointing towards hypercalcemia as it is very common in patients of CA. The symptoms of hypercalcemia are increased thirst, drowsiness and confusion.

Hypercalcemia is the most important finding in all types of malignancies. In myeloma it is especially caused by osteoclast activating factors which increase bone turnover.

The frequency of type-1 diabetes is higher in siblings of diabetic parents (e.g., in the UK 6% by age 30) than in the general population (in the U.K. 0.4% by age 30), while disease concordance in monozygotic (identical) twins is about 40% i.e. the risk that the unaffected twin will develop diabetes.

The patient has hyperthyroidism and its most common cause is Grave’s Disease.
Grave’s Disease is an autoimmune disease due to circulating autoantibodies known as TSH receptor stimulating autoantibodies or Thyroid-stimulating immunoglobulins (TSIs) that bind to and activate thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase the synthesis of thyroid hormone.

The management of patients with diabetes and nephropathy necessitates attention to several aspects of care. Importantly, glycaemic control should be optimized for the patient, attaining the necessary control to reduce complications but done in a safe, monitored manner. Screening for development of nephropathy should be performed on a regular basis to identify microalbuminuria or reductions in GFR and if identified, the diabetes regimen should be tailored accordingly. Prevention and treatment of diabetic nephropathy and other complications necessitates a multifactorial approach. From the options provided insulin is the most suitable as sulfonylureas and biguanides are contraindicated in renal failure. Glitazones are known to cause many side effects including fluid retention and oedema. Hence, insulin will be the best option in this scenario.

Patients with diabetes often develop ophthalmic complications, the most common and potentially most blinding of these complications is diabetic retinopathy.
The following are the 5 stages in the progression of diabetic retinopathy:
1. Dilation of the retinal venules and formation of retinal capillary microaneurysms.
2. Increased vascular permeability.
3. Vascular occlusion and retinal ischemia.
4. Proliferation of new blood vessels on the surface of the retina.
5. Vitreous haemorrhage and contraction of the fibrovascular proliferation.
The first 2 stages of diabetic retinopathy are known as background or nonproliferative retinopathy. Initially, the retinal venules dilate, then microaneurysms (tiny red dots on the retina that cause no visual impairment) appear. As the microaneurysms or retinal capillaries become more permeable, hard exudates appear, reflecting the leakage of plasma.

Mild nonproliferative diabetic retinopathy (NPDR) or background diabetic retinopathy is indicated by the presence of at least 1 microaneurysm, while neovascularization is the hallmark of Proliferative Diabetic Retinopathy (PDR).

Premature ovarian failure presents before the age of 40 in females with a triad of symptoms: amenorrhea, hypergonadism and low oestradiol. This triad is present in the patient.

The patient has Cushing syndrome suggested by the elevated 24hr urine free cortisol. Hence, the mass is most probably a cortisol secreting adenoma.

It has been determined that HPV infection is the most powerful epidemic factor. This virus is needed, but not sufficient for the development of cervical cancer.
The WHO’s International Agency for Research on Cancer (IARC) classified HPV infection as carcinogenic to humans (HPV types 16 and 18), probably carcinogenic (HPV types 31 and 33) and possibly carcinogenic (other HPV types except 6 and 11).
Tobacco smoking, the use of contraceptives, and the number of births are factors that showed no statistically significant deviations in the studied population compared to other countries in the region, as well as European countries. They have an equal statistical significance in all age groups.

Hypocalcaemia presents with such symptoms. It probably happened due to accidental removal of a parathyroid gland during the thyroid surgery. Hypocalcaemia causes laryngospasm which produces stridor.

The use of hormone replacement therapy (HRT) based on unopposed oestrogen increases the risk of endometrial cancer, and uterine hyperplasia or cancer.
Evidence from randomized controlled studies showed a definite association between HRT and uterine hyperplasia and cancer. HRT based on unopposed oestrogen is associated with this observed risk, which is unlike the increased risk of breast cancer linked with combined rather than unopposed HRT.

Only immunoglobulins are required, as he is already immunized.

Pregnancies affected by T1DM are at increased risk for preterm delivery, preeclampsia, macrosomia, shoulder dystocia, intrauterine fetal demise, fetal growth restriction, cardiac and renal malformations, in addition to rare neural conditions such as sacral agenesis.
Successful management of pregnancy in a T1DM patient begins before conception. Research indicates that the implementation of preconception counselling, emphasizing strict glycaemic control before and throughout pregnancy, reduces the rate of perinatal mortality and malformations.
The 2008 bulletin from the National Institute for Health and Clinical Excellence recommends that preconception counselling be offered to all patients with diabetes. Physicians are advised to guide patients on achieving personalized glycaemic control goals, increasing the frequency of glucose monitoring, reducing their HbA1C levels, and recommend avoiding pregnancy if the said level is > 10%.
Other sources suggest deferring pregnancy until HbA1C levels are > 8%, as this margin is associated with better outcomes.

Hyperthyroid patients show significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and pa(O2) than healthy patients. This may of course lead to misdiagnosis of patients with hyperthyroidism as having hyperventilation syndrome.

The patient is most likely to have Bulimia nervosa. A young girl with a low body mass contributes to the low urea. Hypokalaemia and hyponatraemia are due to vomiting. Her urine sodium is also low.
– In Addison’s diseases, there are low levels of sodium and high levels of potassium in the blood. In acute adrenal crisis: The most consistent finding is elevated blood urea nitrogen (BUN) and creatinine. Urinary and sweat sodium also may be elevated.
– In Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) there is hyponatremia with corresponding hypo-osmolality, continued renal excretion of sodium, urine less than maximally dilute and absence of clinical evidence of volume depletion.

Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index
– Assays for thyrotropin-receptor antibodies (particularly TSIs) almost always are positive.
– Detection of TSIs is diagnostic for Graves disease.
– Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroid peroxidase antibodies, are usually present.
– Other autoantibodies that may be present include thyrotropin receptor-blocking antibodies and anti-sodium-iodide symporter antibody.
The presence of these antibodies supports the diagnosis of autoimmune thyroid disease.
– The radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland.