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Pituitary Gland
Function:
Location:
What regulates pituitary trophic hormones?
- Regulates most other endocrine glands/organs
- in the sella turcia.
- Connected to the hypothalamus via stalk.
- The hypothalamus regulates pituitary trophic hormones
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What are the the cell types and hormones the Anterior Lobe of the Pituitary gland secrete?
- Somatotroph 50% Growth Hormone
- Mammotroph 10-20% Prolactin
- Corticotroph 10-20% Corticotropin (ACTH)
- Gonadotroph 10% Gonadotropins (LH, FSH)
- Thyrotroph 5% thyrotropin (TSH)
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What are some hormones that the posterior lobe of the pituitary gland secrete? What is it composed of?
- Composed of unmyelinated nerve fibers:
- Oxytocin
- Antidiuretic hormone (ADH, aka vasopressin)
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Anterior lobe of Pituitary pathology
Hyperfunction (hyperpituitarism)
what is it's main cause/what is it almost always associated with?
How are the symptoms produced? two ways...
- Almost always associated with adenoma
- Symptoms produced via
- 1. Hormone production (over production)
- 2. Mass effect: Gets so big it compresses surrounding structures. Hypertrophy.
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What happens during hyperfunction (hyperpituitarism) with Adenomas affecting
Prolactin
Growth hormone
Corticopropin
Mixed/gonadotropin/thyrotropin/nonfunctional?
- Prolactin 30%: amenorrhea, infertility, galactorrhea, loss of labido
- Growth Hormone: 17%: Gigantism (prepubertal), acromegaly (adults)
- Corticotropin 14%: Cushing's syndrome (hypercortisolism)
- Mixed, Gonadotropin, Thyrotropin = rare
- Nonfunctional 25%: mass effect
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Anterior Lobe of the Pituitary Gland
Hypofunction (hypopituitarism)
What is it?
Causes?
- Deficiency of one or multiple hormones
- Causes:
- Nonfunctional pituitary adenoma (mass effect)
- Ischemic necrosis: Need over 75% destruction to cause problems
- Ablation/destruction by surgery, radiation or adjacent tumor.
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Manifestations of hypofunction (hypopituitarism)
Growth Hormone
Gonadotropin
Prolactin
TSH
ACTH
- GH: Pituitary dwarfim
- Gonadotropin: major sex hormone regulator, deficiency causes Amenorrhea and infertility in women. Decreased libido, impotence and lack of pubic/axillary hair in men.
- Prolactin: No post partum lactation
- TSH: Hypothyroidism
- ACTH: Hypoadrenalism
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Posterior Lobe of the Pituitary Gland Pathology
Oxytocin: ?
ADH:
- Oxytocin: involved in brith, no significant clinical abnormalitites
- ADH: Functions in kidneys to promote resorption of free water. If there is a decrease in ADH too much water loss through urine can cause diabetes insipidus.
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Thyroid Gland
How does it develop?
Normal histology?
- Develops from an invaginationof endoderm which arises at the base of the tongue, migrates caudally to its location anterior to the thyroid cartilage.
- Histology: Follicles filled with colloid. Glassy, icy, smooth, pink looking.
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Hyperthyroidism
most common causes: (4)
- Graves disease (number 1 cause)
- Ingestion of excessive exogenous thyroid hormone (TH) - this happens when someone has hypothyroidism and take too much TH = overcompensate.
- Hyperfunctional multinodular goiter
- Hyperfunctional thyroid adenoma
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Hyperthyroidism:
Diagnosis:
Clinical manifestations? (2 main ones)
- Diagnosis: elevated TH and decreased TSH (primary hyperthyroidism)
- Clinical manifestations: Hypermetabolic state and overactivity of the sympathetic nervous system.
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How does the thyroid gland regulate the body?
Manifestations of Hyperthyroidism (8)
- Thyroid gland is like the thermostat of the body, regulator of energy, mood and other organ functions.
- Hyperthyroid people = hypermetabolic state, increase sympathetic nerve activity.
- heat intolerance
- weight loss despite increased appetite
- irritability
- muscle weakness
- diarrhea
- tachycardia
- congestive heart failure
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What is a thyroid Storm
- Abrupt onset of hyperthyroidism
- patients can die of cardiac arrhythmia due to sudden onset of aggressive hyperthyroidism or it goes undiagnosed for a while.
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Grave's Disease:
Gender predominance?
What is it?
Manifestations? (3)
- Female predominance, common, 5F:1M
- Autoimmune disease where thyroid is overactive producing excessive amounts of thyroid hormones. Has a significant genetic component
- Manifestations:
- 1. Hyperthyroidism
- 2. Exophthalamos (40%) buldging of the eye out of the socket, bug eyes
- 3. Skin lesions: pretibial myxedema pink thickening/scaly skin over tibia.
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Graves Disease:
Autoimmune significant genetic component?
Pathology:
enlargement of what?
Hyperplasia or what?
Increase/decrease of serum components?
- Autoimmune disease where autoantibodies attack TSH receptor so it's constantly stimulated secreting TH
- Pathology:
- diffuse enlargement of the thyroid on gross examination
- Hyperplasia of follicles with lymphoid infiltrates
- Increase in serum-free TH, decreased serum TSH
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Hypothyroidism:
Common causes (3)
- Ablation by surgery or radiation therapy (removal of thyroid/damage by radiation)
- Hashimoto thyroiditis: autoimmune disease, inflammation of the thyroid.
- Iodine deficiency: Was more of a problem before iodine was common in the diet.
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Hypothyroidism: Clinical Manifestations
Cretinism?
Myxedema?
Serum TSH?
- Cretinism: Children with hypothyroidism, rare, iodine in diet prevents this (it's caused by iodine deficiency). Impaired development of skeleton and CNS (mental problems) coarse facial features.
- Myxedema: Adults, generalized apathy, mental sluggishness, listless, cold-intolerance, obese, coarse facial features, enlargement of tongue, deepening of voice, constipation, late cardiac effects.
- Serum TSH: Increased TSH due to loss of feedback inhibition (thyroid can't detect it). Not increased in cases caused by primary hypothalamic or pituitary disease.
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Hashimoto Thyroiditis:
Gender predominance?
Common cause of what disease?
What is it/how is it caused?
Patients at risk for other autoimmune disease?
- Female predominance, older women, significant genetic component 10-20F:1M
- Common cause of hypothyroidism
- Autoimmune; progressive destruction of gland: initially euthyroid (normally) progress to hypothyroid.
- Patients usually at risk for other autoimmune disease and B-cell Non-Hodgkin lymphomas
- No established risk of development of thyroid neoplasm.
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Goiters: what is it?
most common manifestation of what?
Impaired synthesis of what? What is their cause?
Clinical features are due to what effect?
- Goiters are enlargements of the thyroid. They reflect impaired synthesis of thyroid hormone.
- Most often due to iodine dietary deficiency, some idiopathic
- most common manifestation of thyroid disease.
- Most common clinical features are due to mass effect: cosmetic problem, airway obstruction, dysphagia, compression of vessels.
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Hyperfunctional, "toxic" goiter
what is it, how is it caused?
- In a minority of patients with goiters, a "toxic" nodule may develop in a long-standing non-toxic goiter.
- Hyperthyroidism causes goiters
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Thyroid Neoplasms:
Common?
benign or malignant?
genetic/environmental factors?
- Thyroid nodules are common
- Most nodules are non-neoplastic disease
- 1% are carcinomas
- Noducles in males and young patients are more likely to be neoplastic
- Genetic and environmental factors: exposure to radiation in first 2 decades of life.
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What are 5 types of thyroid neoplasms?
- Follicular adenoma
- Papillary thyroid carcinoma
- Follicular carcinoma
- Anaplastic thyroid carcinoma
- Medullary thyroid carcinoma
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Thyroid Neoplasms: Papillary Thyroid Carcinoma
cause of thyroid cancer?
radiation exposure?
genetic mutation of what genes?
Pathology?
Indolent lesions
- most common of thyroid cancers, peak 3-5th decade F>>M
- Some cases related to radiation exposure
- RET proto-oncogene mutation
- Pathology:
- Microscopically characterized by papillary projections
- nuclear clearing - orphan annie nuclei
- nuclear grooves
- Indolent lesions, 10 year survival rates >95%
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Thyroid Neoplasms: Follicular Thyroid Carcinoma
% of thyroid cancers
age?
dietary affect?
resembles?
characteristic?
- 10-20% of thyroid cancers
- Older age than papillary
- Occurs in areas with dietary iodine deficiency
- May resemble a follicular adenoma
- must see invasion through the capsule or into the blood vessels.
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Thyroid Neoplasm: Medullary Thyroid Carcinoma
common?
Derived from what cells?
Sporadic or familial?
Mutation in what genes?
serum affects?
- Uncommon 5% of thyroid cancer
- Derive from the parafollicular (C) cells: which produce calcitonin (acts in opposition to parathyroid hormone)
- May be sporadic or familial: Component of MEN syndromes.
- All have mutation in the RET proto-oncogene
- Increased serum calcitonin
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Parathyroid Glands:
how many glands?
What are the two types of cells and what do they secrete?
- 4 glands located at each pole of the thyroid
- Chief cells: secrete PTH
- Oxyphil cells: unknown function.
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Hyperparathyroidism:
What does PTH do?
Patients with hyperparathyroidism develop what?
- PTH activates osteoclasts: breakdown bone and increase serum calcium concentrations.
- Patients with hyperparathyroidism develop skeletal changes. Ground glass appearance, brown tumor.
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Primary Hyperparathyroidism:
Cause?
clinical features:
- Caused by adenoma or hyperplasia causing hypercalcemia: very common
- Clinical features/symptoms:
- more common in women, often clnically silent
- Bones, stones, groans, moans!
- weakness and fatigue
- Metastatic calcifications: deposition of calcium throughout body, including blood vessels.
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Secondary Hyperparathyroidism:
most common cause: describe mechanism
Symptoms dominated by what?
- Renal failure
- Symptoms dominated by renal disease: decreased phosphate excretion causes hyperphophatemia depresses serum calcium levels stimulates parathyroid glands.
- Normally kidneys would increase vit D synthesis to increase Ca absorption in gut, but they're not working so reduced intestinal absorption of calcium.
- symptoms as in primary, renal osteodystrophy.
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Hypoparathyroidism:
common?
Causes?
Clinical manifestations (4)
- uncommon
- Causes: surgical removal, congenital absence (DiGeorge's syndrome), autoimmune.
- Clinical manifestations: hypocalcemia, increased neuromuscular excitability, cardiac arrhythmias, increased intracranial pressure and seizures.
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Endocrine Pancreas
What are Islets of Langerhans
Cell types? (4)
Exocrine pancreas makes what enzymes?
- Islets of Langerhans: clusters of endocrine cells interspersed among the acinar groups (that make up the exocrine pancreas.
- Cell types:
- Beta: 70% insulin
- Alpha: 20% glucagon
- Delta: 10% somatostatin
- PP 1-2% pancraetic polypeptide
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Diabetes Mellius:
What is it?
what is it's main pathology/effect?
common?
Leading cause of what disease?
- Group of metabolic disorders resulting in hyperglycemia due to defects in insulin secretion, insulation action or both.
- Vasculopathy: with long-term complications involving the kidneys, eyes, nerves and blood vessels.
- 21 million americans affected
- leading cause of ESRD (endstage renal disease, blindness and amputation.
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Classification of Diabetes
Type 1:
Type 2:
- Type 1: aka juvenile, insulin dependent, 10% of cases, severe insulin deficiency.
- Type 2: aka adult onset, non-insulin dependent. Peripheral resistance to insulin action and inadequate response to insulin secretion by Beta cells.
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Presenting symptoms of DM Type 1
what is the main/worse symptom.
- usually presents by age 35
- polyuria
- polydyspia
- polyphagia with weight loss
- Ketoacidosis: fat is primary energy source, excess ketones produced because of fat metabolism, decreases blood pH can lead to diabetic coma.
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Presenting symptoms of DM type 2
- Usually presents after age 40
- Polyuria and polydipsia may occur
- diagnosis made after routine blood tests
- enhanced susceptibility to infection: periodontal disease
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Laboratory diagnosis of Diabetes Mellitus:
Normal glucose range
DM indicated if...
Blodd glucose concentration is higher than?
Fasting glucose is greater than?
Blood glucose is greater than ___ with in 2 hours of ingesting 75g of glucose.
- Normal glucose is 70-120mg/dL
- Random blood glucose concentration of 200mg/dL or higher
- Fasting glucose greater than 126mg/dL on more than one occasion.
- Blood glucose greater than 200mg/dL within 2 hours of ingesting 75g of glucose.
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Etiology of Type 1 Diabetes Mellitus:
- Absolute lack of insulin secondary to autoimmune destruction of B-cells
- Genetric susceptibility + autoimmune factors + environmental insult.
- abrupt onset
- Patients require insulin from outside sources to survive.
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Etiology of Type 2 Diabetes Mellitus:
- Multiple genes play a role: each has its own risk and modified by the environment.
- peripheral tissues cannot respond properly to insulin (insulin resistance)
- B-cell dysfunction: inadequate insulin secretion in the face of insulin resistance and hyperglycemia.
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Disposing factors to Type 2 Diabetes Mellitus:
3 main ones
- 1. Obesity: 80% are obese, 60% exhibit glucose intolerance, adipose tissue appears to be antagonistic to insulin.
- 2. Pregnancy
- 3. Stress.
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Manifestations of DM
what is the big problem/effect of DM?
what are the affects on the pancreas?
- Vasculopathy: Big thing is vascular disease, occurs because of sugar problems. Responsible for 80% of DM-related deaths. Atherosclerosis, MI, gangrene of lower extremities, thickend basement membrane, especially around small blood vessels (MICROANGIOPATHY)
- Pancreas: destruction of islets of langerhans, heavy inflammatory infiltrate, amyloid.
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Manifestations of DM on the Kidneys?
rank of cause of death?
Diffuse glomerulosclerosis?
Nodular Glomerulosclerosis?
- 2nd leading cause of death behind vaculopathy
- Glomerular lesions
- Diffuse glomerulosclerosis: 90% of diabetics within 10 years, not specific to diabetics, microangiopathy around glomerular capillaries and depsotion of matrix. Proteinuria, total renal failure.
- Nodular glomerulosclerosis: 35% specific to diabetics, ball-like deposition of matrix, total renal failure.
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Mainfestations of DM to the eye?
- 4th leading cause of blindness
- Microangiopathy and microaneurysms
- Retinal detachment and vision loss.
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Islet Cell Tumors:
Common?
What part of the pancreas is affected?
Insulinoma?
Gastrinoma?
- uncommon
- Most are from the exocrine pancreas.
- May be functional or non-functional
- Insulinoma occurs.
- Gastrinoma: 90-95% of patients with really bad peptic ulcers.
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What is Zollinger-Ellison Syndrome?
Pancreatic islet cell tumor, hypersecretion of gastric acid causing severe peptic ulcers. 60% malignant.
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Islet Cell Tumors:
What is Insulinoma?
- Insulinoma (Insulin secreting Islet Cell tumor)
- Insulinoma: B-cell tumor, hyperinsulinism, most are adenomas. Hypoglycemia quickly occurs from fasting or exercise. Many are asymptomatic, 5-10% malignant. Nervousness, confusion, stupor. Tx: Surgical excision.
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Adrenal Gland:
Adrenal Cortex: 3 zones, what they secrete
Adnreal Medulla: what it secretes
- Adrenal Cortex
- zona glomerulosa: mineralcorticoids (aldosterone)
- zona fasciculata: glucocorticoids (cortisol)
- zona reticularis: sex hormones (estrogen/androgen)
- Adrenal Medulla: neural origin, chromaffin, source of catecholamines (epinephrine).
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Hypercotisolism (aka?)
Causes: 4
- (cushing syndrome)
- 1. Excess administration of exogenous glucocorticoids (most common): taking stroids, adrenal cortex atrophy.
- 2. Primary adrenal hyperplasia or neoplasm (adrenal adenoma).
- 3. Primary pituitary source (cushing disease): ACTH over-secretion, tumor in pituitary, skin pigmentation.
- 4. Ectopic ACTH secretion by neoplasm, eg lung.
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Hypercortisolism:
Signs and Symptoms:
Speed of onset?
blood pressure? weight? weakness? bone? infection?
- Usually gradual onset.
- hypertension, weight gain (moon faces, buffalo hump), muscle weakness, osteoporosis, increased risk of infection, menstrual irregularities, hirsutism, mental disturbances.
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Hyperaldosteronism:
cause: symptoms?
Primary:
Secondary:
- caused by sodium retention, potassium excretion: producing hypertension and hypokalemia.
- Primar: very rare, hyperplasia of adrenal gland, neoplasm, idiopathic, decreased levels of plasma renin.
- Secondary: Aldosterone release in response to activation of renin-angiotensin system. Increased levels of plasma renin leading to aldosterone release.
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Hypoadrenalism:
decrease in what? because of deficiency of what hormone?
what % of gland needs to be destroyed for affect?
Manifestations?
- Can be primary or secondary: Secondary-decreased stimulation of adrenals from deficiency of ACTH. Need 90% of gland to be destroyed before you see symptoms.
- Manifestations: weakness, fatigue, GI disturbances, anorexia, nausea, vomiting, weight loss, diarrhea.
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Acute Adrenocortical Insufficiency:
How is it caused?
symptoms?
- In patients maintained on exogenous steroids... rapid withdrawal of steroids or failure to increase steroids in response to an acute stress can precipitate an adrenal crisis.
- Also caused by adrenal hemorrhage or stress in a patient with existing Addison's disease.
- Symptoms: Vomiting, abdominal pain, hypotension, coma, death.
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Primary Chronic Adrenocortical Insufficiency (Addison's Disease).
What is it?
Serum hormone level of what?
- An autoimmune disease usually which causes the progressive destruction of the adrenal cortex.
- Serum ACTH may be elevated causing skin and mucosal pigmentation.
- Destruction of cortex prevents response to ACTH.
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Causes of Addison's disease
4 things
- 1. Autoimmune destruction of steroid-producing cells: most common 60-70% of cases.
- Also caused by
- 2. AIDS
- 3. TB
- 4. Metastatic disease
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Secondary Adrenocortical Insufficiency:
What is it?
Symptoms?
What is the big difference in symptoms vs Addison's disease?
- Any disorder of the hypothalamus or pituitary that reduces output of ACTH.
- Symptoms similar to Addison's disease.
- BUT NO skin/mucosa pigmentation because of decreased ACTH.
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Adrenal Neoplasms:
What is Pheochromocytoma?
neoplasm of what cells?
Main symptom, other symptoms?
Rule of 10's?
- Pheochromocytoma: neoplasm of chromaffin cells which make way too much epinepherine therefore causing HYPERTENSION.
- F>M, 30-60 years old.
- Symptoms: Hypertension! tachycardia, tremor, headache.
- Rule of 10's. 10% bilateral, 10% extra-adrenal 10% malignant, 10% familial syndroms. (KNOW THIS)
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Multiple Endocrine Neoplasia (MEN) syndrom.
Types?
What is it?
Gene affected?
- Types MEN 1, 2A, 2B
- Tumors of Multiple Endocrine Organs: Medullary thyroid carcinoma, parathyroid, pheochromocytoma, pancreas, pituitary.
- Caused by: RET proto-oncogene: germ line mutation causes these tumors.
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Multiple Endocrine Neoplasia Syndrome:
MEN 2B
Where are the neuromas?
What are the symptoms?
Whats the persons body look like?
- Mucosal neuromas (tongue, labial commisure, eyelids)
- Large blubbery lips.
- Marfanoid body habitus.
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