HYPOTHYROIDISM ( HASHIMOTO'S THYROIDITIS)

HYPOTHYROIDISM

Is defined as a decrease of thyroxine (T4) and increase of Thyroid stimulatin hormone (TSH), accompanied by certain symptoms.

CONGENITAL HYPOTHYROIDISM

Occurs in about 1/4000 newborns, but is only diagnosed in 10% of them. As well as there are increase of TSH and T4 decrease, the main symptoms include: umbilical hernia, hypotonia, nutrional feeding problems, jaundice, enlarged of the tongue and delayed bone maturation.

AUTOIMMUNE HYPOTHYROIDISM

There are two phases: Hashimoto's thyroiditis and the atrophic thyroiditis. In the first, there are limphocityc infiltrate, a little fibrosis and coloid decrease. In the last one, there are no coloid, much fibrosis and less lymphocytic infiltrate. Is caused by auto-antibodies against Thyroperoxidase (TPO), Thyroglobuline (Tg) and TSH receptor (TSH-R). There are many evidences too, of genetic factor that may contribute to the disease, like HLA-DR and CTLA-4 mutations that can be predisposing for develope hashimoto's thyroiditis. The rubella infection is a well documented factor that can ellicit the disease, as well as the iodine excess like a risk factor.

About antibodies, TPO and Tg are in major patients and works like autoimmune markers, but can exist TSH-R antibodies that block the TSH link to receptor and ellicit hypothyrodism in 10% of patients. Rarely, can coexist TSH-R antibodies and TSI (Grave's antibodies) that bring a fluctuating situation for the patient, between hyper and hypothyroidism. Something important is that TPO and Tg antibodies don't cross the placenta, so they are not going to cause damage in the fetal thyroid. The principal warning for women who is planning be pregnant is to control her disease beacause there is a high risk for mental retard in children.

Clinical features

SYMPTOMS
The main symptoms of hypothyroidism include: weakness, tiredness, hair loss, cold sensation, hoarse voice, dispnea, constipation, weight gain despite loss of apetite, dificulty concentrating, menhorragia, paresthesia, conductive deafness, dry skin, libido lost.

SIGNS
peripheral edema, mixedema, dry skin, hair loss, nail weak, carpal tunel syndrome, serosity cavity effusions, retarded relax phase usually in the aquilian reflex, cold extremities, madarosis, heterogenous goiter.

Diagnose

The diagnose is usually performed with the hormone values mentioned above, clinical symptoms and TPO Ab + (which are positive in 90%). If there still doubt, it can proceed with FNA (fine needle aspiration) biopsy to confirm the diagnose.

Treatment

The indicated treatment is levothyroxine 1.6g/ Kg of body weight if there is no remanent of thyroid tissue. Aproximately, 100-150mg daily. If there is still thyroid tissue (e.g. graves) is recomended start with lower doses (75-125mg). The goal is reduce TSH to normal levels; this can take 3-6 months aproximately, so is very important to explain it to avoid adherence treatment lost.

Complications

Pseudotumor cerebri in children for prolonged use of levothyroxine but is too rare. Mixedema coma, is a coma induce by a crisis in which there are seizures, apnea and the patient can die, this is a very unusual complication.

SUBLINICAL HYPOTHYROIDISM

Is defined as hormones decrease but with no symptoms added. The indication of treatment is a TSH above 10mU/L, and star with only 25/50 mg. If there is TPO Ab+, the patient is in high risk of develope a overt hypothyroidism.

Another hypothyroidisms: Iatrogenic (e.g. after a thyroidectomy), excessive radioactive I therapy

References: Harrison, Internal medicine, 17 Edition.

Interstitial Nephritis in a Patient Taking Creatine

A NEJM CASE

A previously healthy 20-year-old man presented with a four-day history of nausea, vomiting, and bilateral flank pain that began approximately four weeks after he started taking 5 g of creatine (pure creatine monohydrate, ProPerformance Laboratories, Pittsburgh) orally four times a day. He had stopped the creatine and had not taken any medications or other food supplements. His blood pressure was 140/90 mm Hg. Physical examination revealed dehydration and diffuse abdominal tenderness. His serum creatinine concentration was 1.4 mg per deciliter (124 µmol per liter). A complete blood count and measurements of antistreptolysin O, antinuclear antibodies, and plasma complement C3 and C4 concentrations were normal. Urinalysis revealed 4+ protein and 1+ blood; the urine sediment contained dysmorphic red cells and white-cell casts. A spiral computed tomographic scan revealed no abnormalities in the kidneys or the collecting systems.

The patient was hospitalized and treated with intravenous fluid and pain medication. During hospitalization, his blood pressure rose to 160/100 mm Hg and his serum creatinine concentration rose to a peak value of 2.3 mg per deciliter (203 µmol per liter). Urinary protein excretion was 472 mg per day. A renal biopsy revealed acute focal interstitial nephritis and focal tubular injury; electron microscopy revealed effacement of glomerular foot processes and focal thickening of the basement membrane. The patient's blood pressure, serum creatinine concentration, and urinalysis subsequently became normal.

Shown are a proximal tubule with flattened epithelium (arrowhead) and an interstitial mononuclear infiltrate with interspersed eosinophils (arrows).






DISCUSSION

Creatine intake has been used for all athletes since about 1980's. The indicated use consist of two phases: a loading and maintenance phase. The loading phase is for 5-6 days and consist of 9 grams and a quarter of grape juice (or sugar) in any beverage, one fasting and the other after do the exercise. The maintenance phase consist of 4 grams and the grape juice but only after do the exrecise, not fasting. Hence, one person intaking creatine do the load phase the first week, the maintenance phase between the second and the fourth week, rest 3 weeks and start again. After the fourth month the rest phase could long two weeks. In this case, this young take 20 grams daily but for a month, so he should had stop the first week; this is very usual because some people want to see fast results no matter what the consequences are.

Graves Disease

GRAVES DISEASE

The hyperthyroidism of Graves’ disease is the result of circulating IgG antibodies that bind to and activate the G-protein–coupled thyrotropin receptor.This activation stimulates follicular hypertrophy and hyperplasia, causing thyroid enlargement, as well as increases in thyroid hormone production and the fraction of triiodothyronine (T3) relative to thyroxine (T4) in thyroid secretion (from approximately 20% to as high as 30%). Thyroid-function testing in Graves’ disease typically reveals a suppressed serum thyrotropin level and elevated levels of serum T4 and T3. A suppressed serum thyrotropin level with normal serum levels of T4 and T3 is referred to as subclinical hyperthyroidism. Graves’ ophthalmopathy is clinically apparent in approximately 30 to 50% of patients with Graves’ disease, but it is detected in more than 80% of patients who undergo assessment by means of orbital imaging. Manifestations of ophthalmopathy, which vary in severity and have a course that is typically independent of the thyroid disease, can include proptosis, periorbital edema and inflammation, exposure keratitis, photophobia, extraocular muscle infiltration, and eyelid lag - Von graeffe sign (which can also occur with augmented adrenergic stimulation).

Panel A shows a man with bilateral exophthalmos and marked retraction of the upper eyelid. Panel B shows a woman with mild inflammatory signs and hypotropia in the right eye. Panel C shows a woman with marked edema and redness in the upper eyelid, redness of the conjunctiva, and severe chemosis in the left eye. Panel D shows a man with marked edema and retraction of the eyelid and exophthalmos. Panel E shows a woman with marked redness of the conjunctiva and chemosis. There is marked impairment of movement of the globes, which are unable to follow the examiner's finger; this patient had severe dysthyroid optic neuropathy, which responded dramatically to intravenous glucocorticoids (Cortesy of NEJM)

Clinical manifestations

Semiology Apart


This patient has a lot of graves signs: first et all, a big difuse goiter, probably exophtalmos, eyelid lag ( Von graeffe Sign), Pemberton sign ( yugular ingurgitation when rise up her arms due obstruction) and binocular vision impairment (Moebius sign).

The female-to-male ratio among patients with Graves’ disease is between 5:1 and 10:1. The peak incidence is between 40 and 60 years of age, although the disease can occur at any age.

Tests for Graves’ disease–associated antibodies are useful in the evaluation of some conditions, but they are not usually required for diagnosis or to monitor disease activity

IMAGING

A radioiodine-uptake study should be performed in patients in whom painless thyroiditis is considered to be a diagnostic possibility and in patients with an irregular or nodular thyroid gland.

CT is not needed for ophtalmopathy for primary care, and EKG should be performed.

THERAPY

The treatment options for Graves’ disease include antithyroid drugs (propylthiouracil and methimazole), radioiodine, and surgery.

References

- Graves DIsease Review - NEJM

Diarrhea

Diarrhea

Is defined as three or more depositions on a day, or consistence changes making the depositions more fluid and take the recipient form. This last definition is not very useful in clinical practice, so is more common the first one.

Can be classificated according to:

Evolution

Acute: < 2 weeks
Persistent: between 2-4 weeks
Chronic: > 4 weeks

Mechanism

• Osmotic
• Secretory
• Inflammatory
• Malabsortive

Osmotic: Is an acuose diarrhea, very voluminouse, is usually painless, and the most important thing stops in fasting because the causal agent is not being eaten. The most usual agents are cations and anions that can't be taken up by the mucose and causes osmosis with ana elevation of the luminal osmotic presion that elicit diarrhea. The anti-acids ion-containers like phosphates, sulphates and magnesium. Otherway, people with lactase deficiency have abdominal distention, meteorism and diarrhea.

Secretory: Is an acuose diarrhea, very voluminouse, is usually painless and do not stops in fasting. Is caused due to mucose alteration with proteins damage. Is caused by medicaments like AINE's, ACEI, tricyclic anti-depressive's and others. Also is caused by neuroendocrinal tumoration like VIPoma's, Zollinger-Ellison syndrome, carcinoid syndrome. Lastly, bowel disection's like gastrectomy can elicit a secretory diarrhea due to decrease of absortive surface.

Malabsortive: Is steatorrheic, fetid, abdominal distention, and causes nutritional and vitaminic deficiencies. There is three types of diarrhea with malabsortion:

Luminal: in this type, there is deficiency of enzymes or bile acids and digestion is defective. This occurs in pancreatic insuficiency, cyrrhosis and coledocolithiasis.

Mucose: In this type, there is mucose alteration like epitellium atrophy due Celiac Sprue or tropical sprue. Also in Wipple's syndrome there is an infection with t. wipplei that causes absortive epitellium atrophy.

Pos-mucose: is due to lymphatic obstruction in congenital diseases, or tumorations or infections.

in malabsortion, the nutriotional deficiency can reflect as glositis, angular cheilitis, ecchymosis, blur vision, ascites, edema's.

Inflammatory: is a diarrhea accompanied of fever, malaise, abdominal pain, and depositions can be: hematic or not; with mucoid component or not.

IBD (inflammatory bowel disease) is caused principally by Chron's disease and ulcerative colitis. Ulcerative colitis cause edema, erythema and ulceration of the mucose down below right colon, with sigmoid and rectal compromise. Chron's disease cause inflammation since mouth till rectus, with transmural compromise, diferent from ulcerative colitis that only affect the mucose and submucose. Chron's disease can elicit uveitis, arthalgias and aphtas. A classical sign is leukocits present on the coprologic test.

ACUTE ABDOMINAL PAIN

ACUTE ABDOMINAL PAIN

Is an unconfortable pain with onset six hours left, that brings general manifestations in the patient.

Types of pain

Visceral: Is a difuse pain, heavy and can have sympathetic sypmtoms concomitant.
Somatic: Is a localized pain, ellicited with compresion ansd is due to parietal peritoneum inflamation.
Refered: Is a refered pain that occurs in a distal zone from origin, is caused by dermatoma's inervation.
- Shoulder: biliar ways and diapragm.
- Subscapular: Gallblader
- Back: pancreas, gut, peptic ulcer and intestinal obstruction.
- Inguinal and perineal: Nephroplitiasys.

Cholic: Intermitent like cramping, can be urinary or gallblader stones. Peptic ulcer.
Heartbreaking: Very hard pain, can be abdominal arterial disection .
Burning: peptic ulcer, peritonitis and nephrolithiasis.
Alodinia: cutaneous pain with normal stimule. vertebral arthropathy and Herpes zoster.

If there is vomit concomitant:

Bilious vomit: is due to obstruction after the vater ampulla.
Transparent vomit: is due to obstruction before the vater ampulla.
fecaloid: smells, is very dark and is due to intestinal obstruction.
Coffee bar: Is bilious with food remainings, is due to ulcer and tumor.
Food vomit: with food intact is due to pyloric obstruction.
Hematemesis: Is due to esophageal varices and ulceration.

According localization

Epigastrium: pancreatitis, duodenitis, gastritis, peptic ulcer.
Mesogastrium: early appendicitis, pancreatitis, gastroenteritis.
Hipogastrium: Cystitis, prostatitis, diverticulitis.
Right hypochondrium: hepatitis, hepatic abscess, cholangitis, choledocolithiasis, cholecystitis, pancreatitis, peptic ulcer.
Left hypochondrium: Hypersplenism, splenic rupture, splenic infarction, diverticulitis.
Right iliac cavity: appendicitis, pyelonephritis, diverticulitis, Colon CA, salpyngitis, ovaric cyst, endometriosis, ectopic pregnance.
Lef iliac cavity: the same in the right cavity but appendicitis.

Pain characteristics:

• - If there is remision of the pain when vomiting occurs --> peptic ulcer and intestinal obstruction.
• - If the pain is worst during inspiration --> gallblader disease
• - If there is remision of the pain sitting or in mahometan position --> pancretitis
• - If the pain is worst when cought --> inflamation
• - If the food ingest makes worse the pain --> gastric ulcer, if the pain gets better--> duodenal ulcer.
• - If the respiratory movements makes worse the pain--> hepatic abscess, pneumonia, pleuresy.

Rheumatoid Arthritis

Diagnostic Criteria for Rheumatoid Arthritis




Morning Stifness: morning stifness lasting at least 1h since the start of the stifness till the complete remision.

Arthritis in three or more joints: Arthritis in three or more joints regions of the fourteen following: metacarpophalageal, proximal interphalageal, wrists, eldbow, knees, anckles and metatarsophalangeal.

Arthritis in the hand: arthritis in the wrist, metacarpophalangeal and proximal interpahlangeal joints.

Symetric Arthritis: The arthritis is symetric and do not affect the lumbar region except the cervical region.

To this part of the list the symptoms has long at least six months.

Rheumatoid Nodules: Subcutaneous nodules in the joints or over bony prominences.

Rheumatic Factor: Rheumatic factor positive and Anti-CCP

Radiographs: Imaging tests indicating rheumatoid arthritis.

If > or = 4 there is Rheumatoid Arthritis diagnose and if the result is 2 the physician cannotexclude the diagnose.

Clinical aspects

There is historical description for rheumatoid arthritis and several presentation forms.

Z deformity: deviation at the wrist with ulnar deviation of the digits, often with palmar subluxation of the proximal phalanges.



Swan-Neck deformity: Flexion of distal interphalangeal joints and extension of metacarpophalangeal joints.

Boutoniere deformity: Extension of the distal interphalangeal joint and flexion of the proximal metacarpophalangeal joint.

Mallet finger: is a swan-neck deformity of the finger with loss of movility and pinch.



Hallux Valgus: is a foot deformity in which the toe has a lateral deviation.




Baker cyst: Is due to accumulation of sinovial fluid of the knee joint in the popliteal region.

SLE - Systemic Lupus Erythematosous

Diagnostic Criteria SLE

Malar Rash: Is a fixed erythema, flat or raised, over the nose, cheeks or forehead.



Discoid rash: Are an erythematous central patches normally raised with keratotic and scaly rims, atrophy scarring may occur.

Renal disorder: Proteinuria > 0.5 g/d, >3+ or cells casts.

Arthralgia: Joint pain in two or more peripheral joints, with tenderness, swelling or effusion.

Photophobia: Rash due UV rays.

Oral ulcers: Oral ulcers usually in the nasopharigeal region or in the oral mucose. Apthous like lessions.

Neurologic Disorder: Seizures or psychosis. Mood change.

Serositis: Pericarditis or pleuritis with effusion.

Cytopenias: Anemia, leukopenia, lymphopenia or thrombocytopenia.

ANA's: Antinuclear antibodies in serum tests or in immunofluorescence test.

Antibodies: Anti-dsDNA, Anti-SM and/or Anti-phospholipids.

If > or = 4 there is high probability to be a SLE patient with 95% sensibility and 75% specifity.

Note: the signs and symptoms could appear at any time of a well documented patient's history.

References

Harrison - Internal Medicine 17º Edition