Basic endocrinology

THYROID GLAND

Thyroid hormone

Thyroid hormone releasing hormone (THRH) is a peptide hormone that is secreted from the hypothalamus to stimulate the secretion of thyroid secreting hormone in the anterior pituitary gland. Its mode of action is via the intracellular Ca2+. The level of THRH will increase in pregnancy and illness.

Thyroid stimulating hormone (TSH) is a peptide or glycoprotein hormone that is secreted by the anterior pituitary gland (the basophil cells) after being stimulated by TRH. It will act on the thyroid gland to stimulate the secretion of T4 (thyroxine hormone) and T3 (triiodothyronine hormone) via the action of cyclic AMP. The level of TSH will increase in illness and pregnancy.

T4 and T3 hormones are amine (steroid like properties) hormones. It is secreted from the thyroid gland from the action of the TSH. T4 and T3 will bind to the nuclear receptor in the cell (nuclear binding) and involves in the cell metabolism and increase in the growth and mental development of the individuals as well as an increase in the catecholamine secretion.

Hyperthyroidism is caused by excessive amount of thyroid hormone production in the blood. The most common causes of hyperthyroidism are caused by Graves disease, toxic multinodular goitre, toxic adenoma, pituitary adenoma - TSH tumour, excess thyroxine hormone ( T4 ), amiodarone, and lithium.

Graves’s disease is accompanied by eye signs which are worst with smoking and radioactive iodine treatment. The patient may present with lid lag, lid retraction, periorbital edema, proptosis, exophthalmos, diplopia and optic nerve compression.

The investigation may reveal low levels of TSH and high level of T4 and T3. The blood investigation may reveal microcytic anaemia.

The characteristic of hyperthyroidism includes, increase in appetite, weight loss,, nervousness , irritability and clubbing, diarrhoea, amenorrhea, atrial fibrillation, tachycardia, cardiac failure, exertional dyspnea, sweaty skin, swelling of the eyelid, loss of hair, pretibial myxoedema, psychosis, proximal myopathy and tremor.

The treatment requires may include beta blocker such as propanol, carbimazole, radioactive iodine and surgery.

Hypothyroidism is caused by reduce production of thyroid hormone. It is caused by an autoimmune disorder such as Hashimoto thyroiditis (anti microsomal antibody), anti thyroglobulin antibodies), subacute thyroiditis, primary atrophic hypothyroidism, iodine deficient area, post thyroidectomy or after radio iodine treatment and drugs such as Carbimazole ( antithyroid medication), lithium, amiodarone and iodine as well as hypopituitarism.

The clinical effect of hypothyroidism may include low appetite, weight gain, lethargy, hoarseness in voice, dry skin, coarse, pale skin, loss of hair, puffy face, bradycardia, pericardial effusion , cardiac failure, depression, carpal tunnel syndrome, poor memory and reflex relax slowly. Constipation and menorrhagia are also common.

The investigation of hypothyroidism may reveal high levels of TSH and low level of T3 and T4 and high level of cholesterol and triglycerides with an evidence of macrocytic anaemia.

There are a lot of causes of thyroid enlargement which includes diffuse thyroid enlargement and nodular thyroid enlargement. The diffuse thyroid enlargement may include simple goitre, pregnancy, iodine deficiency, subacute viral thyroiditis and Hashimoto thyroiditis and Graves’s disease.

Nodular thyroid enlargement may include toxic multinodular goitre, toxic adenoma goitre and thyroid cyst as well as lymphoma, carcinoma and metastases.

Thyroid cancer presents as a lump in the neck. The lump or nodule accounts for 10% of malignant thyroid cancer. There are a few types of thyroid cancer which include, papillary thyroid carcinoma which is the most common an account for 80% of thyroid cancer and benign and the least aggressive. Follicular thyroid carcinoma is aggressive compared to papillary thyroid carcinoma. It is moderately rare. Anaplastic carcinoma is the most aggressive and invasive thyroid carcinoma which is the rarest type of carcinoma. Medullary carcinoma is the carcinoma that arises from C cells. Hashimoto thyroiditis is associated with lymphoma. Thyroid cancer is treated with thyroidectomy as well as radioactive iodine 131.


hypothyroidism on the left sides
hypothyroidism on the left sides
hyperthyroidism / exopthalmus
hyperthyroidism / exopthalmus
thyroid cancer
thyroid cancer


ADRENAL GLAND

Adrenal hormone

Adrenal hormone may include CRH (corticotrophin releasing hormone), ACTH (adrenocorticotrophin hormone) and cortisol. CRH is a peptide hormone secreted from the hypothalamus and acts via an action of the cyclic AMP on the anterior pituitary gland. ACTH is a peptide hormone secreted from the anterior pituitary gland (basophil) and acts via an action of the cyclic AMP on the adrenal cortex (adrenal zona fasciculata). Cortisol is a steroid hormone which is secreted from the adrenal zona fasciculata and acts via the action of the cyclic AMP.

Cushing syndrome / disease is caused by an excessive endogenous secretion of glucocorticoids which leads to symptoms and signs such as obesity , buffalo hump, moon face, hirsutism, acne, bruising, thin skin, hypertension, psychosis and proximal myopathy.

Cushing syndrome is caused by pituitary tumour, adrenal tumour, ectopic ACTH, ectopic CRH and long term use of the steroid.

The investigation may reveal , hyperglycemia, hypokalemia, hypernatremia, osteoporosis, increase in 24 urinary free cortisol , increase in random cortisol level and an increase in plasma ACTH in ectopic cases or pituitary tumour and reduce the ACTH level in adrenal. Further tests may include imaging technique of the adrenal and pituitary and dexamethasone suppression test.

The treatment may include removal of the tumour in the pituitary, adrenal and ectopic tissue. It is followed by bilateral adrenalectomy which may leads to Nelson syndrome and metyrapone and ketoconazole that inhibit the steroidogenesis process.


Adrenal insufficiency / hypoadrenalism are associated with the failure of the adrenal cortex to secret mineralocorticoids and glucocorticoids. The causes of adrenal insufficiency can be divided into primary causes and secondary causes. The primary causes may include autoimmune such as tuberculosis, infection such as CMV in HIV patient, meningococci septicaemia which leads to adrenal haemorrhage (Waterhouse Friderichsen syndrome) and histoplasmosis , infectious causes such as lupus anticoagulant and thrombophilia and inherited causes such as ACTH receptor mutation and adrenoleucodystrophy as well as bilateral adrenalectomy following surgery. The secondary causes of adrenal insufficiency are any disease or disorder disturbing the hypothalamus and pituitary as well as withdrawal of long term steroid intake which suppress the hypothalamus, pituitary adrenal axis.

The symptoms and signs are weight loss, weakness, pigmentation, abdominal pain and hypotension. The symptoms and signs are vague.

The investigation may reveal hypoglycemia, hyperkalemia, hyponatremia and hypocalcemia. There will be an impairment of Synacthen test, presence of antibodies against the adrenal cortex, lymphocytosis and normocytic anaemia.

The treatment may include hormone replacement such as fludrocortisone to replace the function of the mineralocorticoids and hydrocortisone as a glucocorticoid replacement.

Congenital adrenal hyperplasia is a rare inherited disorder/autosomal recessive9 with high level of ACTH and low level of mineralocorticoid and glucocorticoid that leads to all the hormonal precursors are motivated to the production of the androgen which later leads to genital ambiguity and virilisation. 5% of patients with congenital adrenal hyperplasia are presented with 11 hydroxylase deficiencies while 95% of patent with congenital adrenal hyperplasia is presented with the 21- hydroxylase deficiency.

Conn syndrome is caused by bilateral adrenal hyperplasia and adrenal adenoma. Patient with Conn syndrome is presented with hypenatremia, hypokalemia and hypertension as well as metabolic alkalosis. The investigation may reveals,high aldosterone and low renin level and imaging technique of the adrenal . The treatment may include spironolactone and ACE inhibitor as well as adrenalectomy.

Phaeochromocytoma is a tumour of the adrenal medulla that secretes catecholamine in a large amount. Phaeochromocytoma follow the 10 rules which indicate that 10 % of the tumour is malignant, 10 % of the tumour is bilateral, 10 % of the tumour is extra adrenal and 10 % of the tumour is familial. The investigation requires may include urinary catecholamine, MRI and CT scan of the abdomen and Meta iodobenzyl guanidine scan or MIBG scan. Patient with phaeochromocytoma may present with postural hypotension, intermittent and persistent hypertension, headache, tachycardia and palpitation and change in bowel habit, glycosuria and hyperglycemia and weight loss.





Buffalo hump associated with Cushing syndrome
Buffalo hump associated with Cushing syndrome
Cushing syndrome
Cushing syndrome
skin striae due to Cushing syndrome
skin striae due to Cushing syndrome
Addison disease pigmentation
Addison disease pigmentation

PITUITARY HORMONE

Anterior pituitary hormones are hormones which are secreted from the anterior pituitary gland. These hormones may include ACTH (adrenocorticotropin hormone), TSH (thyroid stimulating hormone), LH (Luteinizing hormone) and FSH (follicle stimulating hormone), GH (growth hormone) and prolactin.

Posterior pituitary hormones are hormones which are secreted from the posterior pituitary gland. These hormones are oxytocin and antidiuretic hormone (ADH).

Pituitary tumour is one of the conditions that may lead to various hormonal disturbances. The pituitary tumour may lead to compression of the optic chasm that leads to the bitemporal hemianopia. It also causes the local mass effect as a result of compression of the tumour. 50% of pituitary tumour is a hormone secreting tumour which secret growth hormone and prolactin. Pituitary tumour is divided into microadenoma (tumour sizes less than 1 cm) and macroadenoma (tumour size more than 1 cm). However pituitary tumour has been always benign. The present of pituitary tumour is confirmed by MRI of the pituitary, visual field testing and serum hormonal level.

Panhypopituitarism is a condition that is associated with the deficiency of all pituitary hormones which leads to diabetes insipidus, growth hormone deficiency, hypogonadism, hypothyroidism and adrenal insufficiency. The treatment may include replacement of the entire deficient hormone. The common causes of panhypopituitarism may include empty sella syndrome, craniopharyngiomas, pituitary tumour and metastases, infiltration by tuberculosis and sarcoidosis and pituitary infarction as a result of postpartum haemorrhage ( Sheehan ‘s syndrome ).

Prolactin is one of the anterior pituitary hormones. The secretion of the prolactin is inhibited by dopamine which is secreted by the hypothalamus under the negative control mechanism. The common cause of raising prolactin level may include, the intake of dopamine antagonist such as phenothiazines and metoclopramide, the use of oestrogen therapy in oral contraceptive pills and hormone replacement therapy, pregnancy, epileptic fit (stress), prolactinoma (25 % of all pituitary tumours, larger in men than women and the treatment may include bromocriptine, pituitary irradiation and surgical procedure) and polycystic ovarian syndrome. The clinical features of excess prolactin secretion may include secondary hypogonadism and galactorrhea.


Growth hormone is secreted under the control of growth hormone releasing hormone and somatostatin. Growth hormone is secreted at night in a pulsatile fashion. Growth hormone acts on the action of insulin like growth factor 1 which is produced by the liver. Deficiency of growth hormone may include decrease in exercise tolerance, decrease in energy, reduced in bone density, decrease in muscle mass, increase in lipid or body fat and a reduction in the cardiac output.

The excess secretion/hypersecretion of growth hormone may lead to acromegaly. This condition is indicated by the raised level in the serum insulin growth factor, failed to suppress growth hormone while performing oral glucose tolerance test, MRI of the pituitary and visual field assessment.

On examination, the patient may present with coarsening of the facial feature, enlargement of the hand, hat sizes and feet as well as lower jaw, increase in sweating hyperhidrosis, carpal tunnel syndrome, and athropathy. The patient may also present with hypertension and diabetes mellitus. There is an increase risk from cardiorespiratory mortality, the incidence of left ventricular hypertrophy/ left ventricular dilation or arrhythmias and cases of obstructive sleep apnea. The treatment for acromegaly may include pituitary surgery, octreotide or somatostatin analogue, irradiation of the pituitary and bromocriptine / dopamine agonist.

Sex hormones may include LH or leutinising hormone or FSH or follicular stimulating hormone. Both are secreted by the action of gonadotrophin secreting hormone from the hypothalamus and inhibin which inhibits the production of FSH. In the male, LH will stimulate Leydig cell to produce testosterone and FSH will stimulate the growth of the testicles. In women, FSH will control the development of the follicle and LH will stimulate the production of progesterone and oestrogen. LH may also cause ovulation where the level will surge during the middle of the menstrual cycle. The testosterone and oestrogen will bind to the sex steroid binding globulin. Primary hypogonadal failure is associated with high level of FSH and LH while secondary gonadal failure is associated with low level of FSH and LH.

The male who suffers from hypogonadism may present with a reduction in muscle bulk, loss of hair (male pattern baldness), high pitch voice, loss of libido, loss of ejaculatory function and loss of erection, decrease in the sizes of the testicles and failure of the spermatogenesis. The hypogonadism are caused by primary congenital gonadal disease such as anorchia or klinefelter’s syndrome as well as secondary gonadal failure such as renal failure, hepatic failure, radiotherapy, torsion, castration , hypopituitarism and hyperprolactinemia as well as androgen receptor deficiency.

The female who suffers from hypogonadism may present with osteoporosis, amenorrhea, infertility, dry vagina, dyspareunia, atrophy of the vagina and vulva, small atrophic breast and loss and thinning of the pubic hair. The hypogonadism is caused by partial ovarian failure in cases of systemic illness, anorexia, hypothyroidism, hypothalamopituitary disease, failure of the gonadotrophin and polycystic ovarian syndrome. Total ovarian failure in cases such as removal of the ovary ( oophorectomy), radio/chemotherapy and dysgenesis.

Polycystic ovarian syndrome is caused by the presence of multiple cysts on the ovary. It is presented with obesity, hirsutism, acne, infertility, diabetes, insulin resistance and oligomenorrhoea or amenorrhoea. The blood test may reveal an increase in the androgen level as well as LH level with normal FSH levels. The treatment may include exercising and diet to reduce the number androgen and increase in the number of sex steroid binding globulin. Spironolactone is also prescribed to the patient as well as metformin which stabilize the menstrual cycle and improve the insulin resistance problems.

Gynaecomastia is an enlargement of the breast tissue which mostly affect male. There are few causes of gynaecomastia which includes the intake of certain drugs such as cyproterone, cimetidine, gonadotrophin, digoxin, oestrogen and spironolactone. The pathological causes may include, hyperthyroidism and hypothyroidism, chronic liver disease, starvation and acromegaly, HcG producing tumour (lung and testicular), and adrenal and testicular tumour or oestrogen producing tumour.



Acromegaly
Acromegaly
gynaecomastia
gynaecomastia

DIABETES

The blood glucose level is regulated by a few hormones. In case of high blood glucose level (hyperglycaemia), insulin will reduce the level of glucose by converting glucose to glycogen. In case of low blood glucose level hormones such as glucagon, cortisol, growth hormone, and epinephrine or adrenaline, will increase the level of glucose by converting or breaking down glycogen to glucose.

Insulin is a peptide hormone. It is synthesized in the pancreas. It is a peptide hormone which is synthesized in the form of proinsulin. When there is a need to secrete insulin, the proinsulin is cleaved into C peptide or insulin. Insulin will act on the tyrosine kinase receptor with a short half life. Insulin will play a lot of functions in the synthesized of the glycogen, protein and triglycerides and fat. Insulin will stimulate the uptake of glucose and amino acids by the muscle to synthesize glycogen and protein by the muscle. Insulin also stimulates hepatic fat and glycogen synthesis, Insulin will stimulate adipose tissue to produce triglycerides.

Diabetes is defined by elevation of the venous plasma glucose in > 7 mmol/l while fasting and > 11.1mmol/l on random test with clinical characteristic of diabetes on a single episode. Diabetes also can be defined as the elevation of the venous plasma glucose in > 7 mmol/l while fasting and > 11.1 mmol/l on random test on two separate occasion.

The symptoms of diabetes may include polyuria, polydipsia, weakness, weight loss, visual blurring, increase risk of infection and genital thrush such as balanitis and pruritus vulva.

Diabetes is divided into type 1 diabetes and type 2 diabetes. Type 1 diabetes accounts for 10 % cases of diabetes mellitus. It is an insulin dependent diabetes mellitus with a juvenile onset. Concordance rates for monozygotic twins are 30% and the risk of developing diabetes if both parents suffer from diabetes mellitus is 10%-20%. Type 1 diabetes mellitus is caused by autoimmune destruction of pancreatic islet beta cells which secretes insulin. Most commonly affect Caucasian. Type 1 diabetes mellitus is 90% associated with HLA DR 3 and HLA DR 4.

Type 2 diabetes mellitus account for 85 % cases of diabetes mellitus. It is a non insulin dependent diabetes mellitus with a maturity onset. Concordance rates in monozygotic twins are 80% and 70% - 90% if both parents are diabetic. It is cause of insulin deficiency and an increase in the insulin resistance. There is no association with HLA and commonly affect Asian and African.

Secondary diabetes will account for 5 % of diabetes mellitus. It is associated with pancreatic disorder that leads to insulin deficiency such as pancreatitis, hemochromatosis and pancreatic cancer or the use of certain drugs such as loop diuretics and thiazide diuretics. Other forms of hormonal disturbance may also lead to diabetes mellitus such as acromegaly, glucagonoma, polycystic ovarian syndrome, thyrotoxicosis and Cushing syndrome.

Management of diabetes mellitus depends on the type of diabetes that the patient had. In type 2 diabetes mellitus the treatment may include lifestyle modification such as weight loss, dieting and exercise, follow from the use of oral hypoglycemic agent and insulin as the final result. Type1 diabetes mellitus the patient may suffer from lack of insulin and the only treatment may include insulin replacement technique. Another management technique may include good glycemic control and aiming for the HbA1c to be less than 7%, low sugar and fat diet, considering smoking cessation, reducing the blood pressure to less than 130/75mmHg and aggressive blood pressure control. Other treatments may include monitoring of the renal function and looks for any evidence of proteinuria and retinal screening and regular visit to the podiatry and consider aspirin intake.

The Oral hypoglycemic agent is useful in treating type 2 diabetes mellitus. The oral hypoglycemic agent may Include, metformin, sulphonylureas and glitazone. Metformin will increase the insulin sensitivity and reduce the peripheral absorption of the glucose from the gut. It is useful as the first line of treatment for diabetes. It will not cause any hypoglycemia and will help in reducing the excess weight. It is sometimes use with glitazone and sulphonylureas. However it carries its own side effect such as lactic acidosis, abdominal pain, diarrhea and anorexia and its use is contraindicated in cardiac, renal and hepatic failure. It will be excreted in the urine.

Sulphonylureas may include tolbutamide that is metabolized in the liver and causing hypoglycaemia and rash as well as Gliclazide with duration of action around 10 - 12 hours and metabolized and excreted in the liver and the renal. Another form of sulphonylureas may include glibenclamide with duration of action of 12 -20 hours and metabolized and excreted in the liver and the renal. Chlorpropamide is also one of the sulphonylureas with duration of action of 36 - 48 hours and excreted and metabolized by the renal with the sides effect of flushing due to alcohol intake, cholestatic and SIADH as well as hypoglycemia. Insulin will reduce the peripheral cell resistance to the insulin and increase basal and stimulated insulin secretion. The effect of sulphonylureas will be hindered by the use of loops and thiazide diuretics. This drug may also lead to weight loss.

Glitazones is another drug which will insulin sensitivity. However it will leads to hepatotoxicity, worsening of the heart failure, weight gain and edema. Glitazones will improve the hyperinsulinemia, hypertriglyceridaemia hyperglycaemia and HbA1c. Glitazones will activate the peroxisme proliferator activated protein. Acarbose is another medication that will slow the absorption of carbohydrates.

There are 2 forms of endocrine emergencies related to diabetes mellitus that are diabetic ketoacidosis and hyperosmolar non ketotic coma. Diabetes ketoacidosis is most commonly affect and present in the patient presented with type 1 diabetes mellitus as the initial presentation of the diabetes. It mostly present due to intercurrent illness or ignorance of the insulin therapy. Diabetic ketoacidosis is associated with insulin deficiency which leads to the uncontrollable catabolism. The symptoms of diabetes mellitus may include polyuria, polydipsia, dehydration, vomiting, thirst, loss of consciousness, Kussmaul breathing (deep sigh breathing) and abdominal pain. The investigation may reveal the sign of renal failure, hyperglycaemia, metabolic acidosis, hyperkalemia and ketonuria. The treatment of diabetic ketoacidosis may include initially with intravenous fluid replacement (potassium chloride and saline solution) follow by intravenous dextrose and insulin as well as low molecular weight heparin and treat any precipitating causes.

Hyperosmolar non ketotic state most commonly presents with type 2 diabetes mellitus. It is associated with uncontrollable glucose intake or the intake of loop and thiazide diuretics in person who remain unnoticed regarding their type 2 diabetes status. The patient may present with hyperglycemia and dehydration. Other signs such as hyperkalemia, acidosis and vomiting are rarely present. The treatment may include dehydration as insulin treatment may lead to a dramatic fall of the glucose level.

Hypoglycaemia is condition due to the low level of the blood glucose. The causes of hypoglycemia may include inadequate intake of the glucose, or overdosage of the sulphonylureas and insulin (Diabetic patient). Other causes of hypoglycemia may include malignancy, chronic alcohol abuse, liver failure, post gastrectomy, pituitary failure, adrenal failure, renal failure and end stage renal failure.

Insulinoma is a pancreatic islet cell tumour that presents with recurrent episodes of insulin secretion which leads to persistent hyperglycaemia. The investigation may reveal the low glucose level and high c peptide and insulin. Insulin overdose may lead to low c peptide and high insulin level.

Complication of the diabetes mellitus may include macrovascular complication such as ischaemic heart disease, cerebrovascular disease, myocardial infarction and peripheral vascular disease. The complication depends on the duration of the diabetes, systolic hypertension, age of the patient , proteinuria and hyperlipidaemia,

Microvascular complication is associated with the degree of the poor glycemic control. Nephropathy effect 30 % - 40% of individuals and the most common cause of death of the younger diabetic patient. It is presented with proteinuria that will progress later into end stage renal failure. ACE inhibitor is beneficial in this case.

Retinopathy is also one of the microvascular complications of diabetes and it affects 90% of the diabetic patient. It is the most common cause of blindness of diabetic patient under 60 years old. Proliferative retinopathy affects 60% of patient suffer type 1 diabetes while it affects 20% of patient suffer from type 2 diabetes mellitus.

Neuropathy will affect 70% - 90% if diabetic patient. The presentation varies depending on the severity of the condition; It may lead to erectile dysfunction due to the ischema of the Vasa nervorum. Autonomic neuropathy is another condition that affects the diabetic patient. The patient may present with gastroparesis, gustatory or generalized sweating, Charcot joint, diarrhoea and cardiac failure as well as postural hypotension.

Diabetic mother may suffer from a lot of complication during the pregnancy period which include pre eclampsia, neonatal distress syndrome, polyhydroamnios, neonatal hypoglycaemia, intrauterine death and fetal macrosomia due to a hyperglycemic condition which contributes to the development of fetal hyperinsulinaemia. Poor glucose control during the 4th and 6th week of pregnancy may increase the risk by 4th to 8th fold of fetal malformation.

Gestational diabetes is a form of diabetes that present whiles the patient on the pregnancy period. The risk factor for developing gestational diabetes may include, overweight mother, age more than 25 years old, positive family history and non Caucasian and HIV positive. The glucose will remit post pregnancy. The treatment may include diet and insulin as oral hypoglycaemic may harm the fetus.

Metabolic syndrome is associated with insulin resistance and obesity. Metabolic syndrome is more common in female and male and its effect 25 % of the population and increase with age. The diagnosis of metabolic syndrome may include hyperuricemia, fasting blood glucose > 7 mmol/l, obesity with an abdominal circumference of more than 88 cm in women and 102 cm in men. The patient may also present with elevated fasting serum triglycerides of more than 1.69mmol/l and blood pressure of more than 130/85mmHg as well as low serum high density lipoprotein <1.29 mmol/l female and 1.04mmol/l. The treatment may include the the use of insulin sensitizer ( glitazone and metformin ) and treatment of the dyslipidaemia. The patient may be treated with hypertensive medication and lifestyle modification such as weight loss, exercise and dieting.







metabolic syndrome
metabolic syndrome

More by this Author


Comments 1 comment

Jones 4 years ago

Nice information provided on basic endocrinology..Very well written with explanation..Great videos too..I liked this hub page..Cheers for creating this page around this topic..Job well done..:)

Visit:http://www.fullthrottleondemand.com/

    Sign in or sign up and post using a HubPages Network account.

    0 of 8192 characters used
    Post Comment

    No HTML is allowed in comments, but URLs will be hyperlinked. Comments are not for promoting your articles or other sites.


    Click to Rate This Article
    working